PReD-Bench/PRed-Bench huggingface dataset:
Inhibition of miR-221 influences bladder cancer cell proliferation and apoptosis
Authors: Z-H Zhao
L-D Zhang
H Liu
J-K Chang
J-Q Hou
Journal: European Review for Medical and Pharmacological Sciences (2017)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: JAK-STAT signaling pathway; SOCS3; miR-221; bladder cancer; cell proliferation
Affiliations: Department of Urology, Huaihe Hospital, Henan University, Kaifeng, China. .

Abstract:  Objective: Janus kinase (JAK) - signal transducer and activator of transcription (STAT) signaling pathway participate in cell proliferation and apoptosis. Suppressors of cytokine signaling 3 (SOCS3) are negative regulators of JAK-STAT3. SOCS3 was found significantly declined, while microRNA-221 (miR-221) obviously up-regulated in bladder cancer tissue. Bioinformatics analysis revealed the complementary binding site between miR-221 and 3'-UTR of SOCS3. This study investigated the role of miR-221 in regulating SOCS3/JAK-STAT3 signaling pathway and bladder cancer cell proliferation and apoptosis. Patients and methods: Bladder cancer tumor tissue and para-carcinoma tissue were collected from patients to test miR-221 and SOCS3 expressions. Dual luciferase assay was used to test the targeting regulatory effect of miR-221 on SOCS3. MiR-221, SOCS3, p-JAK1, p-JAK2, and survivin expressions were compared in T24 and HBEC cells. T24 cells were divided into miR-NC, miR-221 inhibitor, pSicoR-blank, pSicoR-SOCS3, and miR-221 inhibitor + pSicoR-SOCS3 groups. Flow cytometry was applied to detect cell apoptosis. EdU staining was adopted to evaluate cell proliferation. Results: MiR-221 significantly increased, while SOCS3 obviously reduced in bladder cancer tissue compared with para-carcinoma tissue. MiR-221 targeted inhibited SOCS3 expression. MiR-221, phosphorylated JAK1 (p-JAK1), phosphorylated JAK2 (p-JAK2), phosphorylated STAT3 (p-STAT3), and survivin levels markedly up-regulated, whereas SOCS3 expression apparently declined in T24 cells compared with that in HBEC cells. MiR-221 inhibitor and/or pSicoR-SOCS3 elevated SOCS3 expression, decreased p-JAK1, p-JAK2, p-STAT3, and survivin levels, enhanced cell apoptosis, and attenuated cell proliferation. Conclusions: MiR-221 elevated, while SOCS3 reduced in bladder cancer tissue. Inhibition of miR-221 suppressed T24 cell proliferation and induced apoptosis by up-regulating SOCS3 expression, lowering JAK-STAT3 signaling pathway activity, and attenuating survivin expression. 

Retracted: Yes

PubPeer comments:
 Figure 3 appears to include a repeated image. *** ![file] , 
 We are looking into this. , 
 Is there an update on this? Seems to be a clear duplication. ,
Reciprocal negative feedback loop between EZH2 and miR-101-1 contributes to miR-101 deregulation in hepatocellular carcinoma
Authors: Qiming Tu
Chunbo Zhuang
Detai Zhang
Xiaobei Wang
Lihua Hu
Mu Liu
Da Huang
Wuhe Shi
Journal: Oncology Reports (2016)
Discipline: CLINICAL MEDICINE
Keywords: miR-101; hepatocellular carcinoma; EZH2; regulation; feedback loop
Affiliations: Department of Clinical Laboratory, Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.

Abstract:  Although the tumor suppressive role of miR-101 is well documented in hepatocellular carcinoma (HCC), how the expression of miR-101 itself is regulated remains elusive. In the present study, we demonstrated that the miR-101 precursor pre-miR-101-1 could be regulated by an important epigenetic regulator, the enhancer of zeste homolog 2 (EZH2). Reporter gene assays revealed that ectopic expression of EZH2 inhibited the transcriptional activities of miR-101-1 promoter. Subsequent analyses revealed that miR-101-1 directly represses the expression of EZH2, and miR-101-1 and EZH2 form a reciprocal negative feedback loop as indicated by the fact that ectopic mature miR-101 could induce endogenous pre-miR-101-1 expression. This mature miR-101-induced pre-miR-101 expression was specific to pre-miR-101-1 and depended on EZH2 activities. Moreover, our results also demonstrated that similar antitumor effects can be achieved either by ectopic miR-101 or EZH2 silencing in HCC cells. These findings show that elevated EZH2 contributes to miR-101 deregulation in HCC and highlight the coordinated role of miR-101 and EZH2 in hepatocarcinogenesis. 

Retracted: No

PubPeer comments:
 Figure 5B. * Red boxes: Two panels appear to show a small overlap. ![file] ,
Inhibition of protein phosphatase 1 stimulates noncanonical ER stress eIF2α activation to enhance fisetin-induced chemosensitivity in HDAC inhibitor-resistant hepatocellular carcinoma cells
Authors: Yu-Lan Yeh
Wei-Wen Kuo
Ming-Cheng Chen
Hsi-Hsien Hsu
Chih-Yang Huang
Chang
Yi-Sheng Liu
Vijaya Padma Viswanadha
Yu-Chun
Po-Hsiang Liao
Chuan-Chou Tu
Journal: Cancers (2019)
Discipline: CLINICAL MEDICINE
Keywords: chemosensitivity; eIF2α; fisetin; hepatocellular carcinoma; protein phosphatase 1.

Abstract:  Hepatocellular carcinoma (HCC) is a common fatal type of malignant tumor that has highly metastatic and recurrent properties. Fisetin is a natural flavonoid found in various vegetables and fruits which exhibits anti-cancer and anti-inflammatory properties, as well as other effects. Thus, we hypothesized that fisetin can act as an adjuvant therapy in cancer or drug-resistant cancer cells, and further investigated the molecular mechanisms underlying the development of drug-resistance in HCC cells. We found that fisetin effectively inhibited the cell viability of not only parental cells but also histone deacetylase inhibitors-resistant (HDACis-R) cells and enhanced the chemosensitivity of HCC cells. Interestingly, fisetin did not induce cell apoptosis through the activation of the endoplasmic reticulum (ER) stress sensor of protein kinase R (PKR)-like endoplasmic reticulum kinase, but rather through the non-canonical pathway of the protein phosphatase 1 (PP1)-mediated suppression of eIF2α phosphorylation. Moreover, fisetin-induced cell apoptosis was reversed by treatment with PP1 activator or eIF2α siRNA in HCC cells. Based on these observations, we suggest that PP1-eIF2α pathways are significantly involved in the effect of fisetin on HCC apoptosis. Thus, fisetin may act as a novel anticancer drug and new chemotherapy adjuvant which can improve the efficacy of chemotherapeutic agents and diminish their side-effects. 

Retracted: No

PubPeer comments:
 two sets of duplicated images are found ![file] , 
 #1 ![file] Thank you for reviewing the report. Regarding the appeal, we will provide raw data to check it again. , 
 It has been reported that two sets of blot figures in Figure 3A,C looked identical in the original published paper [1]. After a careful check, the authors found that the p-eIF2u03b1 band in Figure 3C was mistakenly uploaded, while the other bands are correct. The authors state this was due to carelessness. With the approval of the Editor-in-Chief and the Editorial Office, the authors wish to replace Figure 3C in [1] with an updated version. The original version of Figure 3C is as follows: ![file] and should be replaced with the following version: ![file] The authors apologize for any inconvenience caused and state that the scientific conclusions are unaffected. The original article has been updated. ,
Interaction of G-protein βγ complex with chromatin modulates GPCR-dependent gene regulation
Authors: Amit Vasanji
Russell Desnoyer
Michael Kinter
Sadashiva S Karnik
Zhong-Hui Duan
Sandro Yong
Hamiyet Unal
Suma Kaveti
Rajaganapathi Jagannathan
Anushree Bhatnagar
Journal: PLoS ONE (2013)
Discipline: Multidisciplinary
Keywords: G-protein; GPCR; Gβγ; nuclear functions; chromatin
Affiliations: Department of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.

Abstract:  Heterotrimeric G-protein signal transduction initiated by G-protein-coupled receptors (GPCRs) in the plasma membrane is thought to propagate through protein-protein interactions of subunits, Gα and Gβγ in the cytosol. In this study, we show novel nuclear functions of Gβγ through demonstrating interaction of Gβ(2) with integral components of chromatin and effects of Gβ(2) depletion on global gene expression. Agonist activation of several GPCRs including the angiotensin II type 1 receptor specifically augmented Gβ(2) levels in the nucleus and Gβ(2) interacted with specific nucleosome core histones and transcriptional modulators. Depletion of Gβ(2) repressed the basal and angiotensin II-dependent transcriptional activities of myocyte enhancer factor 2. Gβ(2) interacted with a sequence motif that was present in several transcription factors, whose genome-wide binding accounted for the Gβ(2)-dependent regulation of approximately 2% genes. These findings suggest a wide-ranging mechanism by which direct interaction of Gβγ with specific chromatin bound transcription factors regulates functional gene networks in response to GPCR activation in cells. 

Retracted: No

PubPeer comments:
null, 
 The correction reads:  *The authors would like to correct an error in Fig 4 that was introduced during the preparation of this figure for publication. In Fig 4A the two bottom left panels of H4 duplicate the Gu03b22 panels. The H4 panels in Fig 4A have been corrected. The HDAC5 panel in Fig 4A duplicates the STAT1 panel shown in Fig 5C. The HDAC5 panel in Fig 4A has been corrected. The authors have stated that cropped blots were provided to a colleague to create the finalized image for publication. The error was introduced to Fig 4 at that point in time, and the original blots were not retained because of a change of institution. The authors confirm that these changes do not alter their findings. * Here is the comparison of Figure 4A and 5C with the duplicated panels highlighted with red and blue boxes. The Gb2 panels are duplicated between the 2 figures but they represent the same experiments and are therefore not marked here. ![file] ,
Effect of lncRNA GAS5 on rats with acute myocardial infarction through regulating miR-21
Authors: L Xia
D-Q Wu
F-X Zhang
J-C Zhang
X-N Zhou
S-C Liu
Y Jiang
Journal: European review for medical and pharmacological sciences (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: lncRNA GAS5; acute myocardial infarction; rat model; cardiac function; myocardial tissues
Affiliations: Department of Anesthesiology, Guizhou Provincial People's Hospital, Guiyang, China. .

Abstract:  Objective: The aim of this study was to investigate the effect of long non-coding ribonucleic acid (lncRNA) growth arrest specific 5 (GAS5) on acute myocardial infarction (AMI) model rats and to explore its regulatory mechanism. Materials and methods: The rat model of AMI was established by subcutaneous injection of isoproterenol (ISO). 30 Sprague Dawley (SD) rats were randomly divided into three groups, including Control group, Model group, and lncRNA GAS5 inhibitor [small interfering ribonucleic acid (siRNA) GAS5] group. Hematoxylin and eosin (H&amp;E) staining was used to detect the pathological damage of myocardial tissues in rats of each group. Myocardial cell apoptosis in each group determined via terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. The levels of matrix metalloproteinase (MMP)-2 and MMP-9 in the serum of rats in each group were examined by enzyme-linked immunosorbent assay (ELISA). Reverse transcription-polymerase chain reaction (RT-PCR) was adopted to measure the expression level of miR-21 in rat myocardial tissues. Results: Compared with Control group, rats in Model group had significantly poor cardiac function, serious pathological damage of myocardial tissues, as well as increased apoptosis rate of myocardial cells. Meanwhile, the levels of MMP-2 and MMP-9 were significantly elevated in serum of Model group, while miR-21 level was down-regulated. In comparison with Model group, rats in siRNA GAS5 group exhibited significantly improved cardiac function, alleviated pathological damage to myocardial tissues, as well as decreased apoptosis rate of myocardial cells. Furthermore, the levels of MMP-2 and MMP-9 decreased significantly in serum of siRNA GAS5 group, whereas the expression level of miR-21 in myocardial tissues was down-regulated. Conclusions: SiRNA GAS5 can enhance the cardiac function of AMI model rats, relieve pathological damage, reduce myocardial cell apoptosis, and inhibit the occurrence of myocardial fibrosis. The possible underlying mechanism may be associated with up-regulation of miR-21. 

Retracted: No

PubPeer comments:
 Figure 1.  Comparison of pathological morphology of rat myocardial tissues in each group . I have doubts about the veridicality of these images. ![file] , 
 Dear authors, is this a typo? ![file] ![file] , 
 #1  I have doubts about the veridicality of these images. ImageTwin was able to trace the originals: Fig 2C of  High Glucose-Induced Cardiomyocyte Death May Be Linked to Unbalanced Branched-Chain Amino Acids and Energy Metabolism ([Zhang et al 2018] ). ![file] ,
Establishment and Comparison of Combining Disease and Syndrome Model of Asthma with “Kidney Yang Deficiency” and “Abnormal Savda”
Authors: Wei-Yi Gong
Hua-Liang Jin
Bei Li
Jing-Cheng Dong
Jing Sun
Qing-Li Luo
Xiao Wu
Yi-Jie Du
Muhammadjan Abduwaki
Yu-Bao Lv
Mammat Nurahmat
Journal: Evidence-based Complementary and Alternative Medicine (2013)
Discipline: CLINICAL MEDICINE
Keywords: Rat models; Kidney Yang Deficiency syndrome; abnormal savda syndrome; traditional Chinese medicine; traditional Uighur medicine
Affiliations: Department of Integrative Medicine, Huashan Hospital, Fudan University, Shanghai 200040, China., Department of Integrative Medicine, Huashan Hospital, Fudan University, Shanghai 200040, China, Xinjiang Uighur Medical Training College, Wada, Xinjiang 848000, China

Abstract:  THE STUDY WAS THE FIRST TIME TO ESTABLISH AND COMPARE TWO RAT MODELS OF TWO COMMON SYNDROMES: Kidney Yang Deficiency syndrome (KYDS) in traditional Chinese medicine (TCM) and abnormal savda syndrome (ASS) in traditional Uighur medicine (TUM). Then, we also established and evaluated rat models of combining disease and syndrome models of asthma with KYDS or ASS. Results showed that usage of the high dose of corticosterone (CORT) injection or external factors could successfully establish the KYDS or ASS rat models, and the two models had similar changes in biological characterization, abnormal behaviors, dysfunction of hypothalamic-pituitary-target organ axes (HPTOA), and sympathetic/parasympathetic (S/P) nerve system but varied in different degrees. The rat models of combining disease and syndrome of asthma with KYDS or ASS had either pathological characteristics of asthma such as airway hyperresponsiveness (AHR), airway inflammation, airway remodeling, which were more serious than allergy exposure alone, or the syndrome performance of Kidney Yang Deficiency in TCM and abnormal savda in TUM. These findings provide a biological rationale for further investigation of combining disease and syndrome model of asthma as an effective animal model for exploring asthma based on the theory of traditional medicine. 

Retracted: No

PubPeer comments:
 unexpected image duplication ![file] Disclaimer: These potential image duplications have been detected automatically using ImageTwin http: dx.doi.org 10.1145 3019612.3019875 Although results have been curated, the automatic algorithm may have generated false positive results and cannot take into account all scientific explanations for apparent duplications like stripped and reprobed blots, time series, serial sections and reused controls. ,
Functional role of SIRT1-induced HMGB1 expression and acetylation in migration, invasion and angiogenesis of ovarian cancer
Authors: D-F Liu
P Jiang
R Yang
W Jiang
Journal: European review for medical and pharmacological sciences (2018)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Ovarian cancer; HMGB1; SIRT1; migration; invasion
Affiliations: Department of Medical, Jinan Maternity and Child Care Hospital, Jinan, Shandong, China. .

Abstract:  Objective: Ovarian cancer is a commonly occurred tumor in females. High motility group box-1 protein (HHMB1) is a chromosome-related protein with multiple functions. A recent study revealed critical roles of HMGB1 in occurrence and progression of ovarian cancer. Sirtuin 1 (SIRT1) is a recently identified novel molecule, which regulates acetylation of HMGB1. Whether SIRT1 is involved in migration, invasion or angiogenesis of ovarian cancer is unclear. This study aims to investigate the role of SIRT1-induced HMGB1 acetylation in migration, invasion, and angiogenesis in ovarian cancer. Patients and methods: In ovarian cancer cell line, SIRT1 expression was potentiated. Western blot and immunofluorescence were used to measure HMGB1 expression, acetylation level, and nuclear translocation. Scratch assay and transwell chamber methods were used to examine cell migration and invasion potency. A mouse model with ovarian cancer cell transplantation was generated to measure induced nitric oxide synthase (iNOs) and CD105 expression. Results: Compared to adjacent tissues, ovarian cancer tissues had significantly decreased SIRT1 expression. In ovarian cancer cells, SIRT1 over-expression decreased HMGB1 and acetylation levels, and SIRT1 knockdown facilitated HMGB1 expression and acetylation. SIRT1 over-expression also suppressed nuclear translocation of HMGB1. Meanwhile, SIRT1 could suppress, migration and angiogenesis of ovarian cancer cells via HMGB1. Conclusions: SIRT1 over-expression effectively inhibited HMGB1 expression and acetylation, thus inhibiting ovarian cancer migration, invasion and angiogenesis. HMGB1 modulated behaviors of ovarian cancer via SIRT1. Therefore, SIRT1 might work as a treatment target for managing ovarian cancer migration. 

Retracted: No

PubPeer comments:
 Figure 6. * The left two panels appear to be partial mirror images of each other, while the far left image appears to contain areas that are visible multiple times within the same photo. Boxes of the same color highlight areas that look similar. ![file] ,
Circular RNA circ_0000034 upregulates STX17 level to promote human retinoblastoma development via inhibiting miR-361-3p
Authors: H-F Yuan
H Liu
N Tan
Q-J Zheng
K-J Chen
D Xu
Journal: European review for medical and pharmacological sciences (2020)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Retinoblastoma; circRNAs; circ_0000034; miR-361-3p; STX17
Affiliations: Department of Ophthalmology, Daping Hospital, Army Medical Center of PLA, Chongqing, China. .

Abstract:  Objective: Retinoblastoma (RB) is a common intraocular tumor of infancy and childhood. Circular RNAs (circRNAs) are related to the development of RB. The purpose of this research was to reveal the functional mechanism of circRNA circ_0000034 in RB. Materials and methods: Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) and Western blot were applied to determine the levels of genes. MTT assay and flow cytometry were employed to assess cell proliferation and apoptosis rate, respectively. Furthermore, cell migratory and invasive abilities were measured using the transwell assay. Mouse xenograft was conducted to analyze the effect of circ_0000034 on tumor growth in vivo. Besides, the interaction between miR-361-3p and circ_0000034 or syntaxin 17 (STX17) was predicted by starBase, and then, confirmed by the Dual-Luciferase reporter assay and RNA immunoprecipitation (RIP) assay. Results: The levels of circ_0000034 and STX17 were increased and miR-361-3p level was decreased in RB tissues and cells. Circ_0000034 knockdown suppressed cell proliferation, migration, invasion, autophagy, and tumor growth, and induced apoptosis in RB. Circ_0000034 targeted miR-361-3p and miR-361-3p bound to STX17. Circ_0000034 overexpression and miR-361-3p knockdown reversed the effect of miR-361-3p upregulation and STX17 depletion on the growth of RB cells, respectively. Besides, circ_0000034 elevated STX17 level by repressing miR-361-3p expression. Conclusions: We demonstrated that circ_0000034 knockdown suppressed the development of RB by the modulation of miR-361-3p/STX17 axis. Our findings provided a theoretical basis for the treatment of RB. 

Retracted: No

PubPeer comments:
  Retinoblastoma (RB), a normal intraocular tumor occurring in the retina, is diagnosed in infants and children . A good beginning, though  normal is an odd choice of words.  Written informed consent was provided by all participants. Infants and children were providing written informed consent? ![file] Half the infants and children in this study were older than 60. ,
Exosome-transmitted circular RNA hsa_circ_0051443 suppresses hepatocellular carcinoma progression
Authors: Qi Liu
Hua Wang
Yibiao Ye
Yingyao Quan
Peiheng He
Wei Chen
Jinyu Liang
Liuhua Chen
Shaoyi Fan
Li Huang
Journal: Cancer Letters (2020)
Discipline: CLINICAL MEDICINE
Keywords: Biomarker; Extracellular vesicles; Liver cancer; circRNA; miRNA.
Affiliations: Department of Pancreatobiliary Surgery, The First Affiliated Hospital and Sun Yat-sen Memorial Hospital, Sun Yat-sen University, No. 58, Zhongshan Second Road, Yuexiu District, Guangzhou, 510080, China., Zhuhai Precision Medical Center, Zhuhai People's Hospital, Zhuhai Hospital Affiliated with Jinan University, Zhuhai, 519000, China., The Second Clinical Medical College of Guangzhou University of Chinese Medicine, Guangzhou, 510405, China., Department of Orthopedics, The First Affiliated Hospital and Sun Yat-sen Memorial Hospital, Sun Yat-sen University, No. 58, Zhongshan Second Road, Yuexiu District, Guangzhou, 510080, China., Department of Medical Ultrasonics, The First Affiliated Hospital and Sun Yat-sen Memorial Hospital, Sun Yat-sen University, No. 58, Zhongshan Second Road, Yuexiu District, Guangzhou, 510080, China., Department of Orthopedics, The First Affiliated Hospital and Sun Yat-sen Memorial Hospital, Sun Yat-sen University, No. 58, Zhongshan Second Road, Yuexiu District, Guangzhou, 510080, China. Electronic address: ., Department of Hepato-Billiary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, No. 107, West Yanjiang Road, Yuexiu District, Guangzhou, 510120, China; Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong Higher Education Institutes, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, No. 107, West Yanjiang Road, Yuexiu District, Guangzhou, 510120, China. Electronic address: .

Abstract:  Extracellular communication in the tumor microenvironment is critical. Results of qRT-PCR show that circ-0051443 is significantly lower in the plasma exosomes and tissues from patients with hepatocellular carcinoma (HCC) than healthy controls. Compared with the producer cells, circ-0051443 is mainly packaged into exosomes. A receiver operating characteristic curve (ROC) shows that the patients with HCC can be distinguished from the controls by exosomal circ-0051443. The role of exosomal circ-0051443 in HCC was determined by animal and cell analyses. Circ-0051443 is transmitted from normal cells to HCC cells via exosomes and suppresses the malignant biological behaviors by promoting cell apoptosis and arresting the cell cycle. Exosomal circ-0051443 decreases the weight and volume of the xenograft tumors in nude mice via BAK1 upregulation in these tumors. BAK1 expression is mediated by exosomal circ-0051443 through competitive bound to miR-331-3p. Therefore, exosomal circ-0051443 can serve as a predictor and potential therapeutic target for HCC. 

Retracted: No

PubPeer comments:
 **Figure 4**. Effect of exosomal circ-0051443 on the hepatocellular carcinoma cellular phenotype. FACS analysis of the cell apoptosis: **Two plots were found duplication**: **Blue Boxes** ![file] , 
 **When enlarged**: ![file] ![file] ,
C/EBPbeta at the core of the TGFbeta cytostatic response and its evasion in metastatic breast cancer cells
Authors: Cristina Nadal
Joan Massagué
Roger R Gomis
Catherine Van Poznak
Claudio Alarcón
Journal: Cancer Cell (2006)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Breast cancers; TGFbeta; C/EBPbeta; p15INK4b; c-MYC
Affiliations: Cancer Biology and Genetics Program, Howard Hughes Medical Institute, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.

Abstract:  Breast cancers may evade the growth-inhibitory action of TGFbeta by accumulating defects of unknown nature that selectively eliminate cytostatic gene responses. We found the transcription factor C/EBPbeta to be essential for TGFbeta induction of the cell cycle inhibitor p15INK4b by a FoxO-Smad complex and repression of c-MYC by an E2F4/5-Smad complex in human epithelial cells. These cytostatic responses are selectively missing in metastatic breast cancer cells from half of the patients that we tested. The basis for this loss was traced to an excess of the C/EBPbeta inhibitory isoform LIP. We suggest that C/EBPbeta plays a key role in the coordination of TGFbeta cytostatic gene responses, and its malfunction may trigger evasion of these responses in breast cancer. 

Retracted: No

PubPeer comments:
 ![file] , 
 Is it possible that they ran multiple gels from the same protein lysate? Possibly because tiny INK CDKI proteins and TFs don t fit on the same gel and since journals are restricted by space, it s not realistically possible or practical to include all gels and all controls? , 
 #2 It looks like the issue is of  differential splicing . Splicing in some places in one panel, splicing in different places in another panel. This makes it problematic when thrying to compare the panels. , 
 can you please elaborate on which of the authors conclusions is affected by this splice, in your opinion? As far as I can tell, the answer is  none . The important part of the experiment is comparing - + TGF-b, not comparing the band intensity in one pair of sample to another pair. Or perhaps do you think the point of the experiment does not matter? , 
 #4  Or perhaps do you think the point of the experiment does not matter? That is reversing the normal rules of logic. Figure 5A. more splicing. https: imgur.com sYibdyA One possibility is that there is splicing every second lane. There is clear splicing in the c-MYC and p21CIP1 panels. Splicing is harder to see in the Beta-ACTIN panel. Examples:- 1. clear splicing between lanes 2 and 3 in the p21CIP1 panels, not evident in the Beta-ACTIN panel, 2. clear splicing between lanes 8 and 9 in the c-MYC panel, not evident in the Bet-ACTIN panel. , 
 #1 Splicing in some panels, but not in others continued. ![file] ,
Expression of a self-processing, pathogen resistance-enhancing gene construct in Arabidopsis
Authors: William A Powell
Charles A Maynard
Haiying Liang
Hongyu Gao
Journal: Biotechnology Letters (2005)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: gene cassette; polyprotein; cleavage recognition site; NIa proteinase; Trichoderma harzinum endochitinase
Affiliations: School of Forest Resources, The Pennsylvania State University, University Park, PA 16802, USA.

Abstract:  A gene cassette, p35S-CNO, was designed to express three gene products driven by a single constitutive CaMV 35S promoter. The individual coding regions were linked in frame to produce a single polyprotein, using spacer sequences encoding a specific heptapeptide cleavage recognition site (ENLYFQS) for the nuclear-inclusion-a (NIa) proteinase of tobacco etch virus (TEV). The protein coding sequences used were: a Trichoderma harzinum endochitinase, a truncated NIa proteinase of TEV, and a wheat oxalate oxidase. When p35S-CNO construct was tested in Arabidopsis thaliana, the polyprotein was properly cleaved after translation and the products exhibited functional enzymatic activity in vivo. 

Retracted: No

PubPeer comments:
 Figure 2: *in vivo* GUS and OxO activity assay. Images of T6 amd T25 appear to be much more similar than expected (red boxes). Could the authors please check? ![file] ,
Rotenone-induced oxidative stress and apoptosis in human liver HepG2 cells
Authors: M P Kashyap
N N Farshori
J Ahmad
S Jahan
M Ahamed
J Musarrat
M A Siddiqui
Q Saquib
A A Al-Khedhairy
Journal: Molecular and Cellular Biochemistry (2013)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Rotenone; neurodegeneration; oxidative stress; cytotoxicity; apoptosis
Affiliations: Department of Zoology, College of Science, King Saud University, P.O. Box 2455, Riyadh, 11451, Saudi Arabia, .

Abstract:  Rotenone, a commonly used pesticide, is well documented to induce selective degeneration in dopaminergic neurons and motor dysfunction. Such rotenone-induced neurodegenration has been primarily suggested through mitochondria-mediated apoptosis and reactive oxygen species (ROS) generation. But the status of rotenone induced changes in liver, the major metabolic site is poorly investigated. Thus, the present investigation was aimed to study the oxidative stress-induced cytotoxicity and apoptotic cell death in human liver cells-HepG2 receiving experimental exposure of rotenone (12.5-250 μM) for 24 h. Rotenone depicted a dose-dependent cytotoxic response in HepG2 cells. These cytotoxic responses were in concurrence with the markers associated with oxidative stress such as an increase in ROS generation and lipid peroxidation as well as a decrease in the glutathione, catalase, and superoxide dismutase levels. The decrease in mitochondrial membrane potential also confirms the impaired mitochondrial activity. The events of cytotoxicity and oxidative stress were found to be associated with up-regulation in the expressions (mRNA and protein) of pro-apoptotic markers viz., p53, Bax, and caspase-3, and down-regulation of anti-apoptotic marker Bcl-2. The data obtain in this study indicate that rotenone-induced cytotoxicity in HepG2 cells via ROS-induced oxidative stress and mitochondria-mediated apoptosis involving p53, Bax/Bcl-2, and caspase-3. 

Retracted: No

PubPeer comments:
 Figure 8. * Red boxes: The Bcl-2 panel in Figure 8C looks similar to the 180 degrees rotated caspase-3 panel in Figure 8D. Reported to the journal in October 2015, with a friendly reminder in 2017, but no response as of today. ![file] ,
Functional analysis of prognostic gene expression network genes in metastatic breast cancer models
Authors: Helen T Michael
Farhoud Faraji
Kent W Hunter
Jeffery E Green
Ngoc-Han Ha
Renard C Walker
Thomas R Geiger
Loren Rodriguez
R Mark Simpson
Journal: PLoS ONE (2014)
Discipline: Multidisciplinary
Keywords: Co-expression networks; genes; connectivity; metastasis; breast cancer
Affiliations: Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America.

Abstract:  Identification of conserved co-expression networks is a useful tool for clustering groups of genes enriched for common molecular or cellular functions [1]. The relative importance of genes within networks can frequently be inferred by the degree of connectivity, with those displaying high connectivity being significantly more likely to be associated with specific molecular functions [2]. Previously we utilized cross-species network analysis to identify two network modules that were significantly associated with distant metastasis free survival in breast cancer. Here, we validate one of the highly connected genes as a metastasis associated gene. Tpx2, the most highly connected gene within a proliferation network specifically prognostic for estrogen receptor positive (ER+) breast cancers, enhances metastatic disease, but in a tumor autonomous, proliferation-independent manner. Histologic analysis suggests instead that variation of TPX2 levels within disseminated tumor cells may influence the transition between dormant to actively proliferating cells in the secondary site. These results support the co-expression network approach for identification of new metastasis-associated genes to provide new information regarding the etiology of breast cancer progression and metastatic disease. 

Retracted: No

PubPeer comments:
 Figure 7C. The shCtrl and shTPX2#1 DAPI and E-Cadherin panels appear to be identical. The Actin and Merge panels are not, so this might be a figure assembly error. Could the authors please check? ![file] , 
 #1 Dr. Bik, you are absolutely correct. Those images are clearly duplicated. I have gone back to the original data and confirmed that we have the correct images for those samples, so the most likely explanation is that the figure was incorrectely assembled. I have regenerated the figure with the original images, which I have attached to this reply, and have also sent an inquiry to the journal about publishing a correction. Thank you for catching this error, and my apologies for not having found this post previously. -Kent Hunter , 
 Dear Dr. Hunter, thank you for your reply and your work in starting a correction with the journal. Much appreciated. Elisabeth Bik ,
Tissue-engineered nerve grafts using a scaffold-independent and injectable drug delivery system: a novel design with translational advantages
Authors: Xiaosong Gu
Yanxi Liu
Shusen Cui
Shuangjiang Yu
Rangjuan Cao
Journal: Journal of Neural Engineering (2019)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: nerve conduits; tissue-engineered nerve grafts; neurotrophic factors; scaffold-independent drug delivery system; methoxy-poly (ethylene glycol)-b-poly(γ-ethyl-L-glutamate)
Affiliations: Department of Hand Surgery, China-Japan Union Hospital, Jilin University, Changchun, People's Republic of China.

Abstract:  Objective: Currently commercially available nerve conduits have demonstrated suboptimal clinical efficacy in repairing peripheral nerve defects. Although tissue-engineered nerve grafts (TENGs) with sustained release of neurotrophic factors (NTFs) are experimentally proved to be more effective than these blank conduits, there remains a lack of clinical translation. NTFs are typically immobilized onto scaffold materials of the conduit via adsorption, specific binding or other incorporation techniques. These scaffold-based delivery strategies increase complexity and cost of conduit fabrication and lack flexibility in choosing different drugs. Therefore, to facilitate clinical translation and commercialization, we construct a TENG using a scaffold-independent drug delivery system (DDS). Approach: This study adopted a scaffold-independent DDS based on methoxy-poly (ethylene glycol)-b-poly(γ-ethyl-L-glutamate) (mPEG-PELG) thermosensitive hydrogels that undergo sol-to-gel transition at body temperature. In addition, TENG, a chitosan scaffold filled with nerve growth factor (NGF)-loaded mPEG-PELG that gel in the lumen upon injection during surgery and function as a drug-releasing conduit-filler, was designed. Subsequently, the efficacy of DDS and therapeutic effects of TENG were assessed. Main results: The results demonstrated that NGF-loaded mPEG-PELG controllably and sustainably released bioactive NGF for 28 d. When bridging a 10 mm rat sciatic nerve gap, the morphological, electrophysiological, and functional analyses revealed that NGF-releasing TENG (Scaffold + NGF/mPEG-PELG) achieved superior regenerative outcomes compared to plain scaffolds and those combined with systemic delivery of NGF (daily intramuscular injection (IM)), and its effects were relatively similar to autografts. Significance: This study has proposed a TENG using thermosensitive hydrogels as an injectable implant to controllably release NGF, which has promising therapeutic potential and translatability. Such TENGs obviate the need for conduit modification, complex preloading or binding mediators, therefore they allow the ease of drug switching in clinical practice and greatly simplify the manufacturing process due to the independent preparation of drug delivery system. 

Retracted: No

PubPeer comments:
 Fig.8D and Fig.8E got same result! ![file] , 
 #1 These are not identical. ![file] ,
ZRANB2 and SYF2-mediated splicing programs converging on ECT2 are involved in breast cancer cell resistance to doxorubicin
Authors: Frédéric Pouzoulet
Martin Dutertre
Didier Auboeuf
Iris Tanaka
Clara Benoit-Pilven
Olivier Delattre
Olivier Saulnier
Alina Chakraborty
Dalila Labiod
Ivan Bièche
Stéphan Vagner
Sophie Vacher
Eric W F Lam
Journal: Nucleic Acids Research (2020)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: alternative splicing; AS regulatory pathways; anticancer drug resistance; doxorubicin; breast cancer
Affiliations: Institut Curie, PSL Research University, CNRS UMR 3348, F-91405 Orsay, France., Paris Sud University, Paris-Saclay University, CNRS UMR 3348, F-91405 Orsay, France., Equipe Labellisée Ligue Contre le Cancer., Institut Curie Research Center, SIREDO Oncology Center, Paris-Sciences-Lettres Research University, INSERM U830, Laboratory of Biology and Genetics of Cancers, Paris, France; Université Paris Diderot, Sorbonne Paris Cité, France., CNRS UMR 5239, Ecole Normale Supérieure de Lyon, Lyon, France., Unité de Pharmacogénomique, Service de génétique, Institut Curie, Paris, France; Université Paris Descartes, Paris, France., Institut Curie, PSL Research University, Translational Research Department, Experimental Radiotherapy Platform, Orsay, France., Imperial College London, London, UK.

Abstract:  Besides analyses of specific alternative splicing (AS) variants, little is known about AS regulatory pathways and programs involved in anticancer drug resistance. Doxorubicin is widely used in breast cancer chemotherapy. Here, we identified 1723 AS events and 41 splicing factors regulated in a breast cancer cell model of acquired resistance to doxorubicin. An RNAi screen on splicing factors identified the little studied ZRANB2 and SYF2, whose depletion partially reversed doxorubicin resistance. By RNAi and RNA-seq in resistant cells, we found that the AS programs controlled by ZRANB2 and SYF2 were enriched in resistance-associated AS events, and converged on the ECT2 splice variant including exon 5 (ECT2-Ex5+). Both ZRANB2 and SYF2 were found associated with ECT2 pre-messenger RNA, and ECT2-Ex5+ isoform depletion reduced doxorubicin resistance. Following doxorubicin treatment, resistant cells accumulated in S phase, which partially depended on ZRANB2, SYF2 and the ECT2-Ex5+ isoform. Finally, doxorubicin combination with an oligonucleotide inhibiting ECT2-Ex5 inclusion reduced doxorubicin-resistant tumor growth in mouse xenografts, and high ECT2-Ex5 inclusion levels were associated with bad prognosis in breast cancer treated with chemotherapy. Altogether, our data identify AS programs controlled by ZRANB2 and SYF2 and converging on ECT2, that participate to breast cancer cell resistance to doxorubicin. 

Retracted: No

PubPeer comments:
 https: twitter.com GaetanBurgio status 1275750892596162561 ,
Delta mtDNA4977 is more common in non-tumoral cells from gastric cancer sample
Authors: Mohammad Hassan Hosseini Akbari
Massoud Houshmand
Behnam Kamalidehghan
Patimah Ismail
Mehdi Shafa Shariat Panahi
Journal: Archives of medical research (2006)
Discipline: CLINICAL MEDICINE
Keywords: mtDNA4977; gastric cancer; mutation; tumoral cells; non-tumoral tissues
Affiliations: Department of Medical Genetics, National Institute for Genetic Engineering and Biotechnology, Tehran, Iran.

Abstract:  Background: The aim of this study was to determine the frequency of delta mtDNA4977 in tumoral cells as compared with adjacent normal cells in gastric cancer. Methods: In order to investigate whether a high incidence of mutation exists in mitochondrial DNA of gastric cancer tissues, we screened one of common region of the mitochondrial genome by PCR amplification and Southern blot followed by DNA sequence analysis. DNA isolated from these cells was used to amplify hypervariable regions ATPase8/6, COXIII, ND3, ND4 and ND5 of delta mtDNA4977. Results: In 107 cancer patients, delta mtDNA4977 was detected in 6 cases (5.60%) of the tumoral tissues and 18 cases (16.82%) of the non-tumoral tissues that were adjacent to the tumors. Levels of delta mtDNA4977 deletions were found to be more in non-tumoral tissues than in adjacent tumoral tissues. There was no correlation of patients with certain clinical parameters like age, sex, tumor location and tumor size; however, there was an obvious relationship with intestinal-type of gastric cancer. Conclusions: Unknown genetic aspects, ambiguous environmental factors and reactive oxygen species (ROS) can cause the delta mtDNA4977 mutation rate to be increased in gastric cancer. The results suggest that percentage level of delta mtDNA4977 is less common and intolerable in tumoral tissue, probably because of high metabolism and ROS generation. We supposed that the cells initially had delta mtDNA4977 transform to tumoral cells and the existed deletion conferred metabolic disadvantage; thus, cells containing such a mtDNA deletion would be overgrown by other cancer cells without this mtDNA deletion. As a result, the presence of delta mtDNA4977 will be low in tumoral cells. 

Retracted: No

PubPeer comments:
 Figure 2. This paper is part of a growing number of papers by the same senior author on topics related to lipid metabolism and atherosclerosis that contain questionable data and images. Besides manipulations with Western blot images, across these papers, there is a pattern of bar graphs that look too similar but aren t 100% identical. Here is just an example. ![file] , 
 Figure 4. The marked bands appear to be re-used for different experimental conditions. , 
 Figure 4. The marked bands appear to be re-used for different experimental conditions. ![file] ,
Vandetanib (ZD6474) induces antiangiogenesis through mTOR&ndash;HIF-1 alpha&ndash;VEGF signaling axis in breast cancer cells
Authors: Fen Zhang
Shiqing Sun
Shuhong Jiao
Ling Li
Jingkui Yu
Wei Wang
Journal: OncoTargets and Therapy (2018)
Discipline: CLINICAL MEDICINE
Keywords: HIF-1 alpha; VEGF; breast cancer; mTOR; vandetanib.
Affiliations: Department of Oncology, Affiliated Tengzhou Central People's Hospital of Jining Medical University, Zaozhuang, Shandong, China, ., Breast Surgery Department, Affiliated Tengzhou Central People's Hospital of Jining Medical University, Zaozhuang, Shandong, China.

Abstract:  Objective: Vandetanib, also known as ZD6474, has recently been proved to be a clinical drug for cancer by targeting vascular endothelial growth factor receptor 2 (VEGFR2), EGFR, and RET tyrosine kinases. We hypothesized that vandetanib will be a drug candidate for breast cancer treatment by targeting angiogenesis. Materials and methods: Vandetanib was used to treat different breast cancer cell lines, and its effect on growth, apoptosis, and cell cycle was studied by MTT assay and flow cytometry. VEGF level in culture medium was measured by ELISA. Gene expression of mechanistic target of rapamycin (mTOR), hypoxia-inducible factor (HIF)-1 alpha, and VEGF at mRNA and protein level were analyzed by quantitative real-time-PCR and Western blot. The cellular behavior variations were investigated by using wound healing assay, transwell invasion assay, and tubular formation assay as well as experiments in vivo. Result: We found that vandetanib can inhibit breast cancer cell line growth via apoptosis and cell cycle regulation. VEGF secretion decreases upon treatment. Vandetanib can reduce both mRNA and protein level of mTOR, HIF-1 alpha, and VEGF. Angiogenesis assays showed that vandetanib can inhibit wound healing, invasion, and tubular formation in culture. Furthermore, vandetanib inhibited the growth of breast tumor in vivo. Conclusion: In short, our study showed that vandetanib can control angiogenesis of breast cancer in culture via mTOR, HIF-1 alpha, and VEGF signaling pathway. 

Retracted: No

PubPeer comments:
 Something is terrible wrong with the data presented in Figure 5. The tumor sizes showed in Figure 5A are wrong and do not correspond to the acutal tumor size shown in Figure 5B. The tomor sizes in Figure 5B are extreme and are far above the maximum size limit in ethical guidelines. In addition two micrographs have been duplicated and presented as something else in Figure 8. ![file] ,
Apolipoprotein A-IV messenger ribonucleic acid abundance is regulated in a tissue-specific manner
Authors: A van Tol
J Auwerx
G Verhoeven
B Staels
Journal: Endocrinology (1990)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: development; estrogen; thyroid hormone; corticosteroid; fibrate
Affiliations: Department of Developmental Biology, Katholieke Universiteit, Leuven, Belgium.

Abstract:  The influence of development and estrogen, thyroid hormone, corticosteroid, and fibrate administration on apolipoprotein (apo) A-IV mRNA levels in the liver and intestine and on serum or plasma concentrations of apo A-IV was studied in the rat. Treatment of ovariectomized rats with ethinyl estradiol provoked a dose-dependent decrease in liver apo A-IV mRNA levels, whereas intestinal apo A-IV mRNA did not change. The serum apo A-IV concentration decreased in a dose-dependent manner. Administration of L-T4 increased liver apo A-IV mRNA levels more than 2-fold, while n-propylthiouracil (PTU) decreased these levels more than 4-fold. Intestinal apo A-IV mRNA levels remained constant upon L-T4 treatment, but increased after PTU. Change in thyroid hormone levels caused no significant alteration of plasma apo A-IV levels. Hydrocorticsone increased liver and intestinal apo A-IV mRNA levels 2- and 1.5-fold, respectively, without changing plasma apo A-IV. Liver and intestinal apo A-IV mRNA underwent opposite changes during development. Intestinal apo A-IV mRNA decreased gradually during the period of weaning, while liver apo A-IV mRNA was undetectable before day 20 of life and rose to adult levels thereafter. Both L-T4 and hydrocortisone were able to increase liver apo A-IV mRNA prematurely when rat pups were treated from day 9 on. Hypothyroidism induced by PTU, on the other hand, was able to delay the developmental rise in liver apo A-IV mRNA. The hypolipidemic drug clofibrate reduced liver apo A-IV mRNA more than 10-fold without changing the intestinal levels. Plasma apo A-IV decreased by one third. Ethinyl estradiol, thyroid hormones, and clofibrate regulate apo A-IV mRNA abundance in a tissue-specific manner. Only liver, not intestinal, apo A-IV mRNA levels respond to treatment. Furthermore, opposing changes in liver and intestinal apo A-IV mRNA levels occur during development, and thyroid hormones and glucocorticoids are able to accelerate the developmental changes in liver apo A-IV mRNA. 

Retracted: No

PubPeer comments:
 Figure 3: More similar than expected ![file] ,
Phosphorylation by aurora-B negatively regulates survivin function during mitosis
Authors: Simon J Morley
Paul D Andrews
Rachel M Barrett
Rene H Medema
Susanne M A Lens
Sally P Wheatley
Jason R Swedlow
Journal: Cell Cycle (2007)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Survivin; Aurora B kinase; Phosphorylation; Mitosis; Cytokinesis
Affiliations: Genome Damage and Stability Centre, University of Sussex, Falmer, Brighton, UK. 

Abstract:  Survivin operates in a complex with aurora B kinase and is phosphorylated by it on threonine 117 in vitro. Here we ask whether phosphorylation of survivin by aurora B kinase regulates its function during mitosis in vivo. Using a phospho-specific antibody we first establish that survivin is phosphorylated at T117 during mitosis and is present at the midbody during cytokinesis. Next we use two independent RNAi complementation approaches to investigate threonine 117 mutants in survivin depleted cells. Our data suggest that while non-phosphorylatable survivin, survivin(T117A), can substitute for the wild type protein, a phosphomimic, survivin(T117E) cannot restore viability, nor can it complement chromosome congression and spindle checkpoint defects that arise due to depletion of endogenous survivin. Fluorescence imaging and fluorescence recovery after photobleaching analysis suggest that the phosphomimic has reduced affinity for centromeres compared with the non-phosphorylatable form. We conclude that survivin is phosphorylated at T117 during mitosis, and once phosphorylated, dephosphorylation is crucial for chromosome congression and progression into anaphase. 

Retracted: No

PubPeer comments:
  Fig. 5 The cell migration in U251 (a) and U87 (b) after transfected with miR-383 by using the Transwell chamber experiment among the three different groups .  Fig. 7 The cell invasion in U251 (a) and U87 (b) after transfected with miR-383 by using the Transwell chamber experiment in the transfection group compared with the non-transfected control cell group and glioma cells transfected with negative sequence group . ![file] For comparison, Fig 5B from [Xie et al (2017)] . ![file] , 
 ![file] Fig 6A of [Zhang et al (2019)] . ![file] ,