PReD-Bench/PRed-Bench huggingface dataset:
Cloning of two human thyroid cDNAs encoding new members of the NADPH oxidase family
Authors: G Vassart
J E Dumont
X De Deken
D Wang
F Miot
F Libert
S Costagliola
M C Many
Journal: Journal of Biological Chemistry (2000)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: NADPH oxidases; thyroid; H(2)O(2) generating system; cloning; gp91(Phox)/Mox1 gene family
Affiliations: Institut de Recherche Interdisciplinaire, Bruxelles, Belgium.

Abstract:  Two cDNAs encoding NADPH oxidases and constituting the thyroid H(2)O(2) generating system have been cloned. The strategy of cloning was based on the functional similarities between H(2)O(2) generation in leukocytes and the thyroid, according to the hypothesis that one of the components of the thyroid system would belong to the gp91(Phox)/Mox1 gene family and display sequence similarities with gp91(Phox). Screening at low stringency with a gp91(Phox) probe of cDNA libraries from thyroid cells in primary culture yielded two distinct human cDNA clones harboring open reading frames of 1551 (ThOX1) and 1548 amino acids (ThOX2), respectively. The encoded polypeptides display 83% sequence similarity and are clearly related to gp91(Phox) (53 and 47% similarity). The theoretical molecular mass of 177 kDa is close to the apparent molecular mass of 180 kDa of the native corresponding porcine flavoprotein and the protein(s) detected by Western blot in dog and human thyroid. ThOX1 and ThOX2 display sequence similarities of 53% and 61%, respectively, with a predicted protein of Caenorhabditis elegans over their entire length. They show along their first 500 amino acids a similarity of 43% with thyroperoxidase. The corresponding genes of ThOX1 and ThOX2 are closely linked on chromosome 15q15.3. The dog mRNA expression is thyroid-specific and up-regulated by agents activating the cAMP pathway as is the synthesis of the polypeptides they are coding for. In human thyroid the positive regulation by cAMP is less pronounced. The proteins ThOX1 and ThOX2 accumulate at the apical membrane of thyrocytes and are co-localized with thyroperoxidase. 

Retracted: No

PubPeer comments:
null, 
null, 
 #1 Much more similar than expected.  ,
Downregulation of YEATS4 by miR-218 sensitizes colorectal cancer cells to L-OHP-induced cell apoptosis by inhibiting cytoprotective autophagy
Authors: Jindai Zhang
Qiang Fu
Suxia Luo
Jianguo Xie
Yonglei Zhang
Xiaobing Chen
Jing Cheng
Journal: Oncology Reports (2016)
Discipline: CLINICAL MEDICINE
Keywords: Colorectal cancer; microRNAs; miR-218; YEATS4; multidrug-resistant
Affiliations: Department of Gastrointestinal Surgery, Tumor Hospital of Henan Province (The Affiliated Tumor Hospital of Zhengzhou University), Zhengzhou, Henan¬†450008, P.R. China., Department of Medical Oncology, Zhengzhou Central Hospital (The Affiliated Central Hospital of Zhengzhou University), Zhengzhou, Henan¬†450007, P.R.¬†China., Department of Digestive Oncology, Tumor Hospital of Henan Province (The Affiliated Tumor Hospital of Zhengzhou University), Zhengzhou, Henan¬†450008, P.R. China.

Abstract:  Colorectal cancer (CRC) is a leading cause of cancer-related death worldwide. Deregulation of microRNAs (miRNAs) has been reported to participate in CRC progression. In the present study, we observed downregulation of miR-218 and upregulation of YEATS domain containing 4 (YEATS4) in CRC tissues and in multidrug-resistant HCT-116/L-OHP cells compared with these levels in normal tissues and parental HCT-116 cells, respectively. The results indicated that miR-218 overexpression significantly decreased the IC50 value of oxaliplatin (L-OHP) in the HCT-116/L-OHP cells, and suppression of miR-218 significantly enhanced the IC50 of L-OHP in the HCT-116 cells. Flow cytometric analysis showed that miR-218 overexpression alone promoted cell apoptosis in the HCT-116/L-OHP cells, which was further enhanced in response to L-OHP, and miR-218 inhibition decreased cell apoptosis in the HCT-116 cells following treatment with L-OHP. Western blot analysis indicated that, compared with the small increase observed in HCT-116 cells, the relative LC3 II level in HCT-116/L-OHP cells after lysosome inhibition via chloroquine (CQ) was markedly upregulated following L-OHP treatment, suggesting induction of autophagy. Exposure of HCT-116/L-OHP cells to L-OHP after control mimic transfection increased autophagic flux, as reflected by increased LC3 II levels, while miR-218 overexpression partly reversed L-OHP-mediated LC3 II accumulation. Additionally, both miR-218 overexpression and CQ treatment promoted L-OHP-induced HCT-116/L-OHP cell apoptosis. Molecularly, our results confirmed that miR-218 directly targets the YEATS4 gene and inhibits YEATS4 expression. Furthermore, YEATS4 overexpression without the 3'-untranslated region (3'-UTR) restored miR-218-inhibited YEATS4 and LC3 II expression, and abolished miR-218-stimulated cell viability loss and cell apoptosis increase in response to L-OHP. In conclusion, miR-218 sensitized HCT-116/L-OHP cells to L-OHP-induced cell apoptosis via inhibition of cytoprotective autophagy by targeting YEATS4 expression. 

Retracted: No

PubPeer comments:
 When the TEM image of Figure 3f rotate 180 degree, it is identical to the TEM image of Figure S12c.  , 
 #1 Thanks for the comment. As mentioned in the paper, the TEM images belong to a same sample. ,
Downregulation of miR-101-3p by hepatitis B virus promotes proliferation and migration of hepatocellular carcinoma cells by targeting Rab5a
Authors: Ailong Huang
Chengcheng Zou
Jianbo Li
Yiyi Cao
Yanrui Sheng
Sen Wang
Jingnan Zhang
Hua Tang
Journal: Archives of Virology (2014)
Discipline: MICROBIOLOGY
Keywords: RAB GTPase 5A; Rab5a gene; Hepatocellular carcinoma; HBV; microRNA
Affiliations: Key Laboratory of Molecular Biology on Infectious Diseases, Ministry of Education, Chongqing Medical University, 1 Yi Xue Yuan Road, Chongqing, 400016, China.

Abstract:  RAB GTPase 5A (RAB5A), a member of the Rab subfamily of small GTPases, acts as an oncogene and has been associated with various key cellular functions, including cell growth, differentiation, apoptosis and angiogenesis. Recently, it has been reported that the Rab5a gene is involved in the progression of cancer. Hepatocellular carcinoma (HCC) is one of the most common and aggressive cancers, and it is usually associated with persistent hepatitis B virus (HBV) infections. Emerging evidence suggests that HBV alters microRNA (miRNA) expression profiles, but the mechanisms underlying this process have not yet been fully elucidated. Here, we examine how HBV affects the production of miR-101-1, which has been shown to be downregulated in HCC. We found that HBV could repress miR-101-3p by inhibiting its promoter activity. Downregulation of miR-101-3p promoted cancer cell growth and migration, and a specific miR-101-3p inhibitor was able to enhance proliferation and migration. Moreover, we identified Rab5a was one of the target genes of miR-101-3p in HBV-related HCC. Forced expression of miR-101-3p in liver cell lines resulted in a marked reduction of the expression of Rab5a at both the mRNA and protein level by directly targeting the 3'untranslated region of Rab5a. Overexpression of Rab5a resulted in a reversal of the suppression of proliferation and migration of SMMC-7721 cells mediated by miR-101-3p. Taken together, our data show that HBV can downregulate miR-101-3p expression by inhibiting its promoter activity and that downregulation of miR-101-3p promotes HCC cell proliferation and migration by targeting Rab5a. This provides new insights into the mechanisms of HBV-related HCC pathogenesis. 

Retracted: No

PubPeer comments:
 Figure 5: The different protein has same western blot, see red box.  ,
Sec22b regulates phagosomal maturation and antigen crosspresentation by dendritic cells
Authors: Mabel Jouve
Alexandre Bobard
Jost Enninga
Ariel Savina
Nicolas Blanchard
Catarina Moita
Sebastian Amigorena
Ignacio Cebrian
Luis F Moita
Geraldine Visentin
Journal: Cell (2011)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Antigen crosspresentation; dendritic cells; SNARE Sec22b; MHC class I; CD8+ T cell-mediated immunity
Affiliations: Institut Curie, INSERM U932, Immunit√© et Cancer, 26 rue d'Ulm, 75248 Paris Cedex 05, France.

Abstract:  Antigen (Ag) crosspresentation by dendritic cells (DCs) involves the presentation of internalized Ags on MHC class I molecules to initiate CD8+ T cell-mediated immunity in response to certain pathogens and tumor cells. Here, we identify the SNARE Sec22b as a specific regulator of Ag crosspresentation. Sec22b localizes to the ER-Golgi intermediate compartment (ERGIC) and pairs to the plasma membrane SNARE syntaxin 4, which is present in phagosomes (Phgs). Depletion of Sec22b inhibits the recruitment of ER-resident proteins to Phgs and to the vacuole containing the Toxoplasma gondii parasite. In Sec22b-deficient DCs, crosspresentation is compromised after Ag phagocytosis or endocytosis and after invasion by T. gondii. Sec22b silencing inhibited Ag export to the cytosol and increased phagosomal degradation by accelerating lysosomal recruitment. Our findings provide insight into an intracellular traffic pathway required for crosspresentation and show that Sec22b-dependent recruitment of ER proteins to Phgs critically influences phagosomal functions in DCs. 

Retracted: No

PubPeer comments:
 Note that evidence now suggests that the phenotype affecting antigen cross-presentation is due to off-target effects of the Sec22b shRNA. Abstract from the paper [ A critical analysis of the role of SNARE protein SEC22B in antigen cross-presentation ] : Cross-presentation initiates immune responses against tumors and viral infections by presenting extracellular antigen on MHC I to activate CD8+ T cell-mediated cytotoxicity. In vitro studies in dendritic cells (DCs) established SNARE protein SEC22B as a specific regulator of cross-presentation. However, the in vivo contribution of SEC22B to cross-presentation has not been tested. To address this, we generated DC-specific Sec22b knockout (CD11c-Cre Sec22bfl fl) mice. Contrary to paradigm, SEC22B-deficient DCs efficiently cross-present both in vivo and in vitro. Though in vitro shRNA-mediated Sec22b silencing in bone marrow-derived dendritic cells (BMDCs) reduced cross-presentation, treatment of SEC22B-deficient BMDCs with the same shRNA produced a similar defect, suggesting the Sec22b shRNA modulates cross-presentation through off-target effects. RNAseq of Sec22b shRNA-treated SEC22B-deficient BMDCs demonstrated several changes in the transcriptome. Our data demonstrate that, contrary to the accepted model, that SEC22B is not necessary for cross-presentation, cautioning against extrapolating phenotypes from knockdown studies alone. ,
MiR-4299 suppresses non-small cell lung cancer cell proliferation, migration and invasion through modulating PTEN/AKT/PI3K pathway
Authors: J-W Wang
W-B Yang
W-P Zhang
J-L Shi
Journal: European review for medical and pharmacological sciences (2018)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: miR-4299; non-small cell lung cancer; NSCLC; clinical significance; biological roles
Affiliations: Department of Cardiothoracic Surgery, Heping Hospital affiliated to Changzhi Medical College, Changzhi, Shanxi, China. .

Abstract:  Objective: The aim of the present study was to investigate clinical significances and biological roles of miR-4299 in non-small cell lung cancer (NSCLC) PATIENTS AND METHODS: Expression of miR-4299 in NSCLC tissues and matched non-tumor tissues was determined by quantitative real-time PCR (qRT-PCR). The correlations between miR-4299 expression and clinicopathological characteristics and prognosis were also analyzed. MTT assay and Transwell assay were performed to determine the proliferation, migration and invasion. Western blotting was used to examine the expressing patterns of PTEN/AKT/PI3K signaling pathway-related proteins. Results: We found that the expression level of miR-4299 was downregulated in NSCLC tissues and cell lines. Low miR-4299 expression was positively correlated with TNM stage (p=0.002), histological grade (p=0.002) and lymph node metastasis (p=0.028). Moreover, Kaplan-Meier survival analysis showed that the patients with low miR-4299 expression had shorter survival time than those with high miR-4299 expression (p=0.0011). More importantly, multivariate analysis suggested that decreased miR-4299 expression was a poor independent prognostic predictor for NSCLC patients (p=0.009). Functionally, overexpression of miR-4299 inhibited the proliferation, migration and invasion in A549 cells. Mechanistically, the results of Western blot showed that miR-4299 exhibited its tumor-suppressive role by modulating PTEN/AKT/PI3K signaling pathway. Conclusions: We firstly indicated that miR-4299 may be a candidate independent marker for NSCLC prognosis and suppressed the progression of NSCLC by modulating the activation of PTEN/AKT/PI3K signaling pathway, suggesting that miR-4299 could be a potential target for developing therapies in treating NSCLC. 

Retracted: No

PubPeer comments:
 Fig 2  C, Transwell analysis was used to determine effect of miR-4299 on migration in A549. D, Transwell analysis was used to determine effect of miR-4299 on invasion in A549 .  I have a concern. ,
Kaempferol promotes apoptosis in human bladder cancer cells by inducing the tumor suppressor, PTEN
Authors: Wei Qiu
Min Zhang
Liqun Zhou
Xuesong Li
Jie Liu
Boxing Su
Feng Xie
Zhongqiang Guo
Ming Su
Journal: International Journal of Molecular Sciences (2013)
Discipline: CHEMISTRY
Keywords: Kaempferol; cancer prevention; apoptosis; bladder cancer; PTEN
Affiliations: Department of Urology, Peking University First Hospital & the Institute of Urology, Peking University, Beijing 100034, China. .

Abstract:  Kaempferol (Kae), a natural flavonoid, is widely distributed in fruits and vegetables. Previous studies have identified Kae as a possible cancer preventive and therapeutic agent. We found Kae to exhibit potent antiproliferation and anti-migration effects in human bladder cancer EJ cells. Kaempferol robustly induced apoptosis in EJ cells in a dose-dependent manner, as evidenced by increased cleavage of caspase-3. Furthermore, we found Kae-induced apoptosis in EJ cells to be associated with phosphatase and the tensin homolog deleted on the chromosome 10 (PTEN)/PI3K/Akt pathway. Kae significantly increased PTEN and decreased Akt phosphorylation. Kae-induced apoptosis was partially attenuated in PTEN-knockdown cells. Our findings indicate that Kae could be an alternative medicine for bladder cancer, based on a PTEN activation mechanism. 

Retracted: No

PubPeer comments:
 Fig 3C.  Kae suppresses migration of EJ cells.... (C) Transwell cell migration assay in EJ cells with DMSO-only or 20 or 40 u03bcM Kae for 48 h . Overlap marked.  , 
 Figure 4. Kae-induced apoptosis in EJ cells involves PTEN.(C) PTEN siRNA inhibits Kae-induced apoptosis. PTEN siRNA-transfected EJ cells treated with 40 u03bcM Kae for 24 h resulted in significantly decreased apoptosis, compared with NC siRNA-transfected cells treated with 40 u03bcM Kae. Data represent the mean u00b1 SD of three independent experiments (**p 0.01 vs. NC + Kae group) duplicated data marked. Seems like different gate used on the same raw FACS data.  ,
HP1Œ± is highly expressed in glioma cells and facilitates cell proliferation and survival
Authors: Hua Guo
Wei Tu
Zhifeng Deng
Xianliang Lai
Xingen Zhu
Journal: Biochemical and Biophysical Research Communications (2017)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Glioma; H3K9 methylation; HP1Œ±; Transcriptional repression.
Affiliations: Department of Neurosurgery, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, China., Department of Neurosurgery, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, China. Electronic address: .

Abstract:  Epigenetic alteration plays critical roles in gliomagenesis by regulating gene expression through modifications of Histones and DNA. Trimethylation of H3K9, an essential repressed transcription mark, and one of its methyltransferase, SUV39H1, are implicated in glioma pathogenesis and progression. We find that the protein level of HP1Œ±, a reader of H3K9me3 is elevated in cultured glioma cell lines and glioma tissues. H3K9me3 is also upregulated. Depletion of HP1Œ± and SUV39H1 weakens glioma cell proliferation capacity and results in apoptosis of cells. Furthermore, we find that HP1Œ± and H3K9me3 are enriched in the FAS and PUMA promoters, which suggests that upregulated HP1Œ± and H3K9me3 contribute to cell survival by suppressing apoptotic activators. These data suggests that up-regulated HP1Œ± and H3K9me3 in glioma cells are functionally associated with glioma pathogenesis and progression and may serve as novel biomarkers for diagnostic and therapeutic targeting of brain tumors. 

Retracted: No

PubPeer comments:
 This paper was also submitted to Cancer Biomarkers, where it was published under doi: 10.3233 cbm-170249. After realizing these were duplicate submission, the Cancer Biomarkers version was later retracted, and the retraction notice can be found here: https: content.iospress.com articles cancer-biomarkers cbm179249 ,
Taurine prevents fructose-diet induced collagen abnormalities in rat skin
Authors: Mambakkam Katchapeswaran Ravichandran
Carani Venkataraman Anuradha
Velusami Thirunavukkarasu
Thirugnanam Anitha Nandhini
Journal: Journal of Diabetes and its Complications (2005)
Discipline: CLINICAL MEDICINE
Keywords: Taurine administration; skin collagen; high-fructose-fed rats; physicochemical properties; glycation

Abstract:  Objective: The aim of the study is to investigate the effect of taurine administration on the content and characteristics of skin collagen in high-fructose-fed rats. Research design and methods: Adult male Wistar rats were divided into four groups of six each: a control group (CON) and a taurine-supplemented control group (CON+TAU), a high fructose diet-fed group (FRU), and a taurine supplemented fructose diet-fed group (FRU+TAU). After 30 days, collagen was isolated from the skin, and its physicochemical properties were studied. Results: Fructose administration caused an accumulation of collagen and extensive cross-linking. This was evidenced by increases in glycation, fluorescence, and peroxidation in collagen samples. The physicochemical properties of collagen, like shrinkage temperature, aldehyde content, solubility pattern, and susceptibility to denaturing agents, were altered in the fructose-fed rats. The sodium dodecyl sulphate-polyacrylamide gel electrophoretic (SDS-PAGE) pattern of collagen from fructose-fed rats showed and elevated beta component of Type I collagen. Simultaneous administration of taurine alleviated these changes. Conclusion: The positive influence of taurine on both collagen content and its properties suggests a potential mechanism for the ability of taurine to delay diabetic complications. 

Retracted: No

PubPeer comments:
 Concern about Figure 3. Several elements appear to be visible in both panels A (Acid soluble collagen) and B (Pepsin soluble collagen).  , 
 Additional concern. Figure 3 appears to also share lots of features with Figure 3 from Thirunavukkarasu et al. - Experimental Diab. Res., 5:237u2013244, 2004 - DOI: 10.1080 154386090506148. See: https: pubpeer.com publications 8E18CF1AD7A63D9B3410635F158781 Could the authors please clarify? This does not appear to be a simple case of grabbing the wrong gel photo by accident.  , 
 There are also many very similar measurements between these 2 papers. Here are some graphs that look unexpectedly similar, with unexpectedly small error bars. Could the authors please provide the raw data?  ,
Piperlongumine induces ROS mediated cell death and synergizes paclitaxel in human intestinal cancer cells
Authors: Harsha Hegde
Vijayashree Nayak
Sugeerappa Laxmanappa Hoti
Laxminarayan Rawat
Journal: Biomedicine & Pharmacotherapy (2020)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Cancer; Herbal medicine; Paclitaxel; Piperlongumine; ROS
Affiliations: Department of Biological Sciences, Birla Institute of Technology and Science, Pilani, K.K. Birla Goa Campus, NH-17B, Zuarinagar, Goa 403726, India. Electronic address: ., ICMR-National Institute of Traditional Medicine, Nehru Nagar, Belagavi, 590010, Karnataka, India. Electronic address: .

Abstract:  Piperlongumine (PL), a herbal drug extracted from long pepper (Piper longum L), is known for its anti-inflammatory and anti-cancer properties. Although, its anti-cancer potential has been evaluated in cancer models like breast, pancreatic, gastric, hepatocellular and lung carcinoma, there is no report on its bio-activity evaluation in intestinal cancers. Here, we report the anti-neoplastic potential of PL against human intestinal carcinoma in-vitro and its possible mechanisms of action. Cytotoxicity studies demonstrate that PL inhibits cell proliferation of INT-407 and HCT-116 cells in a concentration and time-dependent manner. Also, PL elevated the levels of intracellular reactive oxygen species, which may lead to lethal oxidative stress, mitochondrial dysfunction, and nuclear fragmentation. Remarkably, P53, P21, BAX, and SMAD4 were significantly upregulated after PL treatment whereas; BCL2 and SURVIVIN were down-regulated. Moreover, the combination study also shows the synergistic effect of PL with the current chemotherapeutic drug paclitaxel. These findings suggest that PL possesses anti-neoplastic properties in intestinal cancer cells. 

Retracted: No

PubPeer comments:
 This paper makes use of two cell lines described as * INT-407 and HCT-116 intestinal cancer cell lines were obtained from cell repository, National Centre for Cell Science, Pune, India.  * Unfortunatly INT-407 is not an intestinal cancer cell line. It was originally thought to be a normal fetal intestinal cell line but shown in the late 1960s to be a HeLa contaminated cell line. Thus it is a cancerous cell line, but from the uterus cervix, not from the intestine. This invalidate many of the conclusions of this paper, which shows that with increasing doses of piperlongumine (PL)treatment * the number of dead cells increased significantly in both INT-407 and HCT-116 cell lines as compared to respective controls (Fig. 2B and D). These results suggested that PL triggers cell death in intestinal cancerous cells. * As one of the two cell lines has nothing to do with intestinal cancer, the results are not specific to that cancer type. See the relevant [Cellosaurus entry] ,
miR-27a induced by colon cancer cells in HLECs promotes lymphangiogenesis by targeting SMAD4
Authors: Xiu-Ying Xiao
Xiao-Lin Lin
Jin-Lu Tong
Qian Xiao
Chen-Peng Zhang
Qi Xu
Journal: PLoS ONE (2017)
Discipline: Multidisciplinary
Keywords: Metastasis; tumor cells; lymphatic vessels; blood vessels; transcoelomic spreading
Affiliations: Department of Oncology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China., Division of Gastroenterology and Hepatology, Renji Hospital, Shanghai Institute of Digestive Disease, School of Medicine, Shanghai JiaoTong University, Shanghai, China., Department of Nuclear Medicine, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China., Department of Pharmacology, Yale School of Medicine, New Haven, Connecticut, United States of America.

Abstract:  Aim: Metastasis of tumor cells occurs through lymphatic vessels, blood vessels and transcoelomic spreading. Growing evidence from in vivo and in vitro studies has indicated that tumor lymphangiogenesis facilitates metastasis. However, the regulation of lymphangiogenesis in colon cancer remains unclear. The aims of this study were to identify key miRNAs in colon cancer lymphangiogenesis and to investigate its target and mechanism. Methods: miRNA microarray analysis was conducted to identify miRNAs in human lymphatic endothelial cells (HLECs) that were regulated by co-cultured human colon cancer cells. Gain- and loss-of-function studies were performed to determine the function of miR-27a, a top hint, on lymphangiogenesis and migration in HLECs. Furthermore, bioinformatics prediction and experimental validation were performed to identify miR-27a target genes in lymphangiogenesis. Results: We found that expression of miR-27a in HLECs was induced by co-culturing with colon cancer cells. Over-expression of miR-27a in HLECs enhanced lymphatic tube formation and migration, whereas inhibition of miR-27a reduced lymphatic tube formation and migration. Luciferase reporter assays showed that miR-27a directly targeted SMAD4, a pivotal component of the TGF-Œ≤ pathway. In addition, gain-of-function and loss-of-function experiments showed that SMAD4 negatively regulated the length of lymphatic vessels formed by HLECs and migration. Conclusions: Our data indicated that colon cancer cell induced the expression of miR-27a in HLECs, which promoted lymphangiogenesis by targeting SMAD4. Our finding implicated miR-27a as a potential target for new anticancer therapies in colon cancer. 

Retracted: No

PubPeer comments:
 Two images in figure 4D appear to overlap. ***  ,
Direct Hepatocyte Insulin Signaling Is Required for Lipogenesis but Is Dispensable for the Suppression of Glucose Production
Authors: Wenyun Lu
Paul M Titchenell
Julia Chen
William J Quinn
Mingjian Lu
Morris J Birnbaum
Helen Chen
Joshua D Rabinowitz
Bobby R Monks
Qingwei Chu
Changhong Li
Journal: Cell Metabolism (2016)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: insulin-resistant states; type II diabetes mellitus; hepatic glucose production; lipid synthesis; selective insulin resistance
Affiliations: Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA., Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA., Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA., Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: .

Abstract:  During insulin-resistant states such as type II diabetes mellitus (T2DM), insulin fails to suppress hepatic glucose production (HGP) yet promotes lipid synthesis. This metabolic state has been termed "selective insulin resistance" to indicate a defect in one arm of the insulin-signaling cascade, potentially downstream of Akt. Here we demonstrate that Akt-dependent activation of mTORC1 and inhibition of Foxo1 are required and sufficient for de novo lipogenesis, suggesting that hepatic insulin signaling is likely to be intact in insulin-resistant states. Moreover, cell-nonautonomous suppression of HGP by insulin depends on a reduction of adipocyte lipolysis and serum FFAs but is independent of vagal efferents or glucagon signaling. These data are consistent with a model in which, during T2DM, intact liver insulin signaling drives enhanced lipogenesis while excess circulating FFAs become a dominant inducer of nonsuppressible HGP. 

Retracted: No

PubPeer comments:
 Two plates shown in Figure 2C appear to share the same origin, although one has a feature not evident in the other and has been rotated. This suggests the issue was not merely an error during figure assembly. ***  ,
miR-200b regulates breast cancer cell proliferation and invasion by targeting radixin
Authors: Chunyan Guo
Huijun Lu
HaizHong Yu
Jianfen Yuan
Chunhong Xiao
Hong Hong
Zhimei Wu
Journal: Experimental and Therapeutic Medicine (2020)
Discipline: CLINICAL MEDICINE
Keywords: breast cancer; invasion; microRNA-200b; proliferation; radixin.
Affiliations: Department of Clinical Laboratory, Nantong Traditional Chinese Medicine Hospital, Nantong, Jiangsu 226001, P.R. China., Department of Clinical Laboratory, Nantong Tumor Hospital, Nantong, Jiangsu 226361, P.R. China.

Abstract:  Radixin is an important member of the Ezrin-Radixin-Moesin protein family that is involved in cell invasion, metastasis and movement. microRNA (miR)-200b is a well-studied microRNA associated with the development of multiple tumors. Previous bioinformatics analysis has demonstrated that miR-200b has a complementary binding site in the 3'-untranslated region of radixin mRNA. The present study aimed to investigate the role of miR-200b in regulating radixin expression, cell proliferation and invasion in breast cancer. Breast cancer tissues at different Tumor-Node-Metastasis (TNM) stages were collected; breast tissues from patients with hyperplasia were used as a control. miR-200b and radixin mRNA expression levels were tested by reverse transcription-quantitative PCR. Radixin protein expression was detected by western blotting. The highly metastatic MDA-MB-231 cells were divided into four groups and transfected with a miR-negative control (NC), miR-200b mimic, small interfering (si)RNA-NC or siRNA targeting radixin. Cell invasion was evaluated by Transwell assay and cell proliferation was assessed by 5-ethynyl-2'-deoxyuridine staining. Compared with the control group, radixin mRNA expression was significantly higher in breast cancer tissues and increased with TNM stage. miR-200b expression levels exhibited the opposite trend. Radixin mRNA expression in breast cancer cells was notably higher, whereas miR-200b expression was lower compared with that in normal breast epithelial MCF-10A cells. The expression of radixin was higher, whereas miR-200b was lower in MDA-MB-231 cells compared with that in MCF-7 cells. miR-200b mimic or siRNA-radixin transfection downregulated the expression of radixin in MDA-MB-231 cells and attenuated the invasive and proliferative abilities of these cells. miR-200b-knockdown and radixin overexpression were associated with enhanced cell invasion in breast cancer. In conclusion, miR-200b regulates breast cancer cell proliferation and invasion by targeting radixin expression. 

Retracted: No

PubPeer comments:
 Fig 5E.  Radixin overexpression increases breast cancer cell proliferation and invasion. ... (E) Wound-healing assay was performed to analyze cell migration.  The upper right panel rewards closer attention.  I have not checked further. ,
Puma and p21 represent cooperating checkpoints limiting self-renewal and chromosomal instability of somatic stem cells in response to telomere dysfunction
Authors: K Lenhard Rudolph
Tobias Sperka
Zhenyu Ju
Michael R Speicher
Andr√© Lechel
Monika Mach
Zhangfa Song
Yohei Morita
Kodandaramireddy Nalapareddy
Birgit Liss
Luis Miguel Guachalla
Martin D Burkhalter
Yvonne Begus-Nahrmann
Falk Schlaudraff
Journal: Nature Cell Biology (2011)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: p53; Puma; p21; apoptosis; cell-cycle arrest
Affiliations: Institute of Molecular Medicine and Max-Planck-Research Department on Stem Cell Aging, University of Ulm, 89081 Ulm, Germany.

Abstract:  The tumour suppressor p53 activates Puma-dependent apoptosis and p21-dependent cell-cycle arrest in response to DNA damage. Deletion of p21 improved stem-cell function and organ maintenance in progeroid mice with dysfunctional telomeres, but the function of Puma has not been investigated in this context. Here we show that deletion of Puma improves stem- and progenitor-cell function, organ maintenance and lifespan of telomere-dysfunctional mice. Puma deletion impairs the clearance of stem and progenitor cells that have accumulated DNA damage as a consequence of critically short telomeres. However, further accumulation of DNA damage in these rescued progenitor cells leads to increasing activation of p21. RNA interference experiments show that upregulation of p21 limits proliferation and evolution of chromosomal imbalances of Puma-deficient stem and progenitor cells with dysfunctional telomeres. These results provide experimental evidence that p53-dependent apoptosis and cell-cycle arrest act in cooperating checkpoints limiting tissue maintenance and evolution of chromosomal instability at stem- and progenitor-cell levels in response to telomere dysfunction. Selective inhibition of Puma-dependent apoptosis can result in temporary improvements in maintenance of telomere-dysfunctional organs. 

Retracted: No

PubPeer comments:
 2021 correction .... https: www.nature.com articles s41556-021-00633-w Correction to: Nature Cell Biology https: doi.org 10.1038 ncb2388, published online 4 December 2011 In the version of this Letter originally published, in Fig. 4f, the P value for shRNA p21-2 infected HSCs versus control shRNA-infected HSCs from mTerc+ +, Pumau2212 u2212 mice is 0.04 and not non-significant (ns) as indicated in the figure. In the legend for Supplementary Fig. 2e, the correct n values were n = 16u201338 mice per group (16 WT, 16 Pumau2212 u2212, 31 G3mTercu2212 u2212Puma+ +, 38 G3mTercu2212 u2212Pumau2212 u2212) for the analysis of aberrant crypt foci (ACF) and n = 7 mice per group for the analysis of macroscopic tumours. These numbers were swapped in the original figure legend. These two errors do not affect the conclusion or any statement of the publication. ,
LncRNA MEG3 inhibits HMEC-1 cells growth, migration and tube formation via sponging miR-147
Authors: Dongmei Han
Liu He
Jianshi Du
Ying Ma
Dejun Xu
Tianji Liu
Journal: Biological Chemistry (2020)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: HMEC-1 cells; ICAM-1; MEG3; atherosclerosis; miR-147
Affiliations: Department of Vascular Surgery, China-Japan Union Hospital of Jilin University, No. 126 Xiantai Street, Changchun 130033, China., Department of Emergency Medicine, China-Japan Union Hospital of Jilin University, Changchun 130033, China., Department of Anesthesiology, China-Japan Union Hospital of Jilin University, Changchun 130033, China.

Abstract:  Long non-coding RNA (lncRNA) maternally expressed gene 3 (MEG3) has been identified as a regulatory molecule in angiogenesis. The goal of this study was to illustrate how MEG3 affects the angiogenesis of vascular endothelial cells. Expression of MEG3, miR-147 and intracellular cell adhesion molecule-1 (ICAM-1) in human microvascular endothelial cell line (HMEC-1) was altered by transfection, then cell viability, apoptosis, migration, tube formation, as well as the correlation among MEG3, miR-147 and ICAM-1 were explored. MEG3 was down-regulated during tube formation of HMEC-1 cells. MEG3 expression suppressed cells viability, migration and tube formation, while it induced apoptosis. MEG3 could bind with miR-147 and repress miR-147 expression. MiR-147 induced ICAM-1 expression, and contained ICAM-1 target sequences. The anti-atherogenic actions of MEG3 were inhibited by miR-147, and the anti-atherogenic actions of miR-147 suppression were also inhibited when ICAM-1 was overexpressed. Further, ICAM-1 overexpression showed activated roles in Wnt/Œ≤-catenin and Jak/Stat signaling pathways. In low-density lipoprotein receptor (Ldlr)-/- mice, MEG3 overexpression reduced CD68+, CD3+ and ICAM-1 areas in lesions and increased collagen content. MEG3 inhibited HMEC-1 cell growth, migration and tube formation. The anti-atherogenic actions of MEG3 might be mediated via sponging miR-147, and thereby repressing the expression of ICAM-1. 

Retracted: Yes

PubPeer comments:
 Figure 3. Repetitive features appear to be visible in panels a through f.  ,
Long Non Coding RNA SNHG16 Facilitates Proliferation, Migration, Invasion and Autophagy of Neuroblastoma Cells via Sponging miR-542-3p and Upregulating ATG5 Expression
Authors: Yubin Dong
Yi Wen
Chenghe Tang
Xiaohui Gong
Journal: OncoTargets and therapy (2020)
Discipline: CLINICAL MEDICINE
Keywords: ATG5; NB; SNHG16; miR-542-3p.
Affiliations: Neonatal Pediatrics, Central Hospital of Zhoukou City, Zhoukou, Henan, People's Republic of China., Neonatal Pediatrics, Shanghai Children's Hospital, Shanghai, People's Republic of China., Neonatal Pediatrics, First Affiliated Hospital of Xinxiang Medical College, Xinxiang, Henan, People's Republic of China.

Abstract:  Background: Neuroblastoma (NB) is a heterogeneous pediatric malignant tumor with many biological and clinical characteristics. Long non-coding RNA small nucleolar RNA host gene 16 (SNHG16) plays vital role in the development of NB. However, the potential mechanism of SNHG16 in the progression of NB is rarely reported. Methods: The expression levels of SNHG16, miR-542-3p and autophagy-related gene 5 (ATG5) were measured with quantitative real-time polymerase chain reaction (qRT-PCR). The proliferation, migration and invasion of NB cells were determined using 3-(4, 5-dimethylthiazol-2-YI)-2, 5-diphenyltetrazolium bromide (MTT) or transwell assay. Protein levels of ATG5, microtubule-associated protein A1/1B-light chain3 (LC3-I/II) and p62 were detected by Western blot analysis. The interaction between miR-542-3p and SNHG16 or ATG5 was predicted by starBase and confirmed by dual luciferase reporter assay. Xenograft mice models were constructed to confirm the role of SNHG16 in vivo. Results: SNHG16 was upregulated in NB tissues and cells and associated with clinical stage and poor prognosis of NB. Knockdown of SNHG16 impeded proliferation, migration, invasion and autophagy of NB cells in vitro, and suppressed tumor growth in vivo. Interestingly, SNHG16 mediated ATG5 expression through sponging miR-542-3p in NB cells. Moreover, miR-542-3p downregulation reversed the inhibitory effects of SNHG16 silencing on proliferation, migration, invasion and autophagy of NB cells. Besides, ATG5 overturned the regulatory effects on proliferation, migration, invasion and autophagy of NB cells induced by SNHG16 or miR-542-3p knockdown. Conclusion: SNHG16 facilitated proliferation, migration, invasion and autophagy of NB cells via sponging miR-542-3p and upregulating ATG5 expression in NB. 

Retracted: No

PubPeer comments:
 Figure6  ,
The phosphatidylinositol 3-kinase/AKT kinase pathway in multiple myeloma plasma cells: roles in cytokine-dependent survival and proliferative responses
Authors: A Lichtenstein
Y Tu
A Gardner
Journal: Cancer Research (2000)
Discipline: CLINICAL MEDICINE
Keywords: Interleukin 6; insulin-like growth factor I; PI 3-K/AKT pathway; multiple myeloma; plasma cells
Affiliations: Department of Medicine, West LA VA Medical Center, Los Angeles, California, 90073, USA.

Abstract:  Interleukin 6 (IL-6) and insulin-like growth factor I (IGF-I) induce proliferative and antiapoptotic responses in multiple myeloma (MM) plasma cells. Because these cytokines may activate the phosphatidylinositol 3-kinase (PI 3-K)/AKT kinase pathway in other cell types, we investigated the role of PI 3-K/AKT in MM cell responses. IGF-I effectively activated PI 3-K in 8226 and OCI-My5 MM cells, but IL-6 was ineffective. However, IL-6 successfully activated PI 3-K in AF-10 MM cells and IL-6-dependent MH.60 plasmacytoma/hybridoma cells. IGF-I also successfully activated PI 3-K in four of four MM patient specimens, and IL-6 activated PI 3-K in three of four specimens. Inhibition of PI 3-K activity with wortmannin or Ly294002 blocked the antiapoptotic effect of IGF-I and the proliferative effect of IL-6 in the myeloma cell lines. Furthermore, a dominant negative PI 3-K construct, expressed in AF-10 cells by adenoviral infection, also significantly inhibited the IL-6 proliferative response in MM cells. In correlation with activation of PI 3-K, IGF-I also effectively activated the AKT kinase in 8226 and OCI-My5 cells, and IL-6 activated AKT in AF-10 and MH.60 cells. However, although incapable of activating PI 3-K in 8226 and OCI-My5 cells, IL-6 successfully activated AKT in these MM lines, suggesting PI 3-K-independent mechanisms of AKT activation. The prevention of a myeloma cell proliferative response resulting from inhibition of PI 3-K activity was not associated with an inhibition of IL-6-dependent extracellular signal-regulated kinase (ERK) activation. These results support a role for the PI 3-K/AKT pathway in cytokine-dependent responses in myeloma cells, which is independent of any activation of the ERK pathway. 

Retracted: No

PubPeer comments:
 This May 2017 article has been withdrawn in September 2018. The retraction notice gives no further insight as to what has happened. The original paper PDF has been removed from the journal s website, but has been archived here: https: web.archive.org web 20180509192830 https: www.europeanreview.org wp wp-content uploads 2489-2498-Research-on-the-protective-effects-of-antioxidants-on-MS-induced-by-thyroid-dysfunction.pdf ,
STAT1-induced upregulation of lncRNA LINC01123 predicts poor prognosis and promotes the progression of endometrial cancer through miR-516b/KIF4A
Authors: Hongfeng Zhou
Jincai Wang
Wenming Liu
Qingyuan Zhang
Jin Wu
Yuguang Yang
Journal: Cell Cycle (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: KIF4A; LncRNA LINC01123; biomarker; endometrial cancer; metastasis
Affiliations: Department of Medical Oncology, Harbin Medical University Cancer Hospital , Harbin, Heilongjiang, China.

Abstract:  Long non-coding RNAs (lncRNAs) have been proposed as suppressors or promoters in many tumor processes. LncRNA LINC01123 (LINC01123) was a newly identified lncRNA which was firstly functionally analyzed in lung cancer. However, its expression and function in other tumor types were rarely reported. In this study, we firstly confirmed that LINC01123 was highly expressed in both endometrial cancer (EC) tissues and cell lines using bioinformatics analysis and RT-CPR. Then, we preliminarily analyzed the mechanisms involved in overexpression of LINC01123 in EC, finding that STAT1 could bind directly to the LINC01123 promoter region and activate its transcription. Clinical research with 106 patients indicated that high expression of LINC01123 was associated with advanced clinical progression and poor clinical outcome of EC patients. Functionally, knockdown of LINC01123 suppressed the proliferation, migration and invasion of EC cells, and promoted apoptosis. Mechanistically, we observed that LINC01123 may act as an endogenous sponge by competing for miR-516b, thereby regulating KIF4A. Overall, our study revealed a novel LINC01123/miR-516b/KIF4A pathway regulatory axis in EC pathogenesis. LINC01123 may be a novel prognostic biomarker and therapeutic target in EC.Abbreviations: EC: Endometrial cancer; LncRNA: Long non-coding RNA; EMT: epithelial-mesenchymal transition; miRNA: microRNA; qRT-PCR: Quantitative real-time polymerase chain reaction; SPSS: Statistical Package for Social Sciences; Chip: chromatin-immunoprecipitation, TCGA: The Cancer Genome Atlas; CCK-8: Cell Counting Kit-8; KIF4A: Chromosome-associated kinesin KIF4A. 

Retracted: No

PubPeer comments:
 In Figure 3g, a Western blot panel has been duplicated and presented as something else. In addition, two of the primer sequences listed in Table 1 (GAPDH and U6) are incorrect (only Forward primers where tested, with filter for Homo sapiens).  ,
MicroRNA-592 targets IGF-1R to suppress cellular proliferation, migration and invasion in hepatocellular carcinoma
Authors: Lichao Wang
Mao Tang
Longlong Liu
Wenyao Wang
Hongfei Zhang
Zhengfang Zhou
Shaojun Zhang
Journal: Oncology letters (2017)
Discipline: CLINICAL MEDICINE
Keywords: hepatocellular carcinoma; insulin-like growth factor 1 receptor; microRNA-592.
Affiliations: Department of General Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, P.R. China.

Abstract:  MicroRNAs (miRs) can function as tumor suppressors or oncogenes in different types of human malignancy, and may provide an effective therapy for cancer. The expression and functions of miR-592 have previously been studied in relation to cancer. However, the expression and potential functions of miR-592 in hepatocellular carcinoma (HCC) are still unknown. Using quantitative polymerase chain reaction, MTT assays, cellular migration and invasion assays, bioinformatics software, western blot analysis and dual-luciferase report assays, the present study explored the expression and roles of miR-592 in HCC. It was identified that miR-592 was significantly downregulated in HCC tissues and cell lines. The statistical analysis revealed that low expression of miR-592 was evidently associated with tumor node metastasis stage and lymph node metastasis. Additionally, the present study provided the first evidence that miR-592 was likely to directly target the insulin-like growth factor 1 receptor in vitro. The present results indicated that miR-592 could be investigated as an efficacious therapeutic target for HCC in the future. 

Retracted: No

PubPeer comments:
 Image concerns in this paper were found during a systematic search of papers in Spandidos journals for possible duplicated images. Figure 4AB. Several panels appear to show overlapping areas with each other. Boxes of the same color highlight areas that look similar to each other.  , 
 In addition to the possible overlapping areas between panels in Figure 4, there are interesting similarities to panels in Figure 2 of another paper from different authors and a different institute. That paper is: Jingbin Ni, Yisha Yang, Di Liu, Hui Sun, Shimao Jin, Jingying Li MicroRNA-429 inhibits gastric cancer migration and invasion through the downregulation of specificity protein 1t ONCOLOGY LETTERS 13: 3845-3849, 2017, DOI: 10.3892 ol.2017.5869, https: pubpeer.com publications 7B22585C514F22766A1FE32A4C82CE  ,
Retracted Article: Exosomal miR-25-3p derived from hypoxia tumor mediates IL-6 secretion and stimulates cell viability and migration in breast cancer
Authors: Fang He
Shuyang Dai
Jie Zou
Xueming Cao
Zhanjia Yang
Zhou Zhou
Zhengmin Li
Poshi Xu
Journal: RSC Advances (2019)
Discipline: CHEMISTRY
Keywords: Hypoxia; Exosomal miR-25-3p; Breast cancer progression; HIF-1Œ±; IL-6
Affiliations: Department of Medical Laboratory, Fuwai Central China Cardiovascular Hospital, Zhengzhou, China, Operating Room, Woman & Infants Hospital of Zhengzhou, Department of Blood Transfusion, People's Hospital of Zhengzhou, Cardiac Care Unit, Fuwai Hospital, Chinese Academy of Medical Sciences, Beijing

Abstract:  Hypoxia is a major hallmark of solid tumors and is associated with malignant phenotypes. Exosomal miRNAs derived from hypoxia tumor cells are implicated in the modulation of cancer progression, whereas, the mechanisms underlying the association between hypoxia and exosomal miR-25-3p during breast cancer progression remain to be further clarified. The present study aimed to investigate the role of exosomal miR-25-3p in regulating breast cancer progression. Herein, we found that miR-25-3p expression was increased in hypoxia tumor-derived exosomes a HIF-1Œ±-dependent manner. Hypoxia exosomes markedly stimulated the viability and migration of normoxia breast cancer cells, which was reversed by miR-25-3p depletion. Inhibition of exosomes miR-25-3p lowered hypoxic-induced the expression of IL-6 and NF-Œ∫B from THP-1 and RAW264.7 cells in a TLR7/8-dependent way. Treatment of macrophage supernatant (MS) initially incubated with hypoxic-responsed exosomes accelerated the viability and migration of breast cancer cells, and miR-25-3p depletion relieved the stimulatory effects of hypoxic on cell viability and migration. Moreover, miR-25-3p knockdown dramatically suppressed HIF-1Œ±-induced tumor growth in vivo via inactivation of IL-6/STAT3 signaling pathway, reflected by the abated abundances of IL-6 and p-STAT3. These data suggested that absence of exosomal miR-25-3p rescued breast cancer aggressiveness through inhibiting cell viability and migration by regulation of IL-6 secretion from macrophages, providing a potential biomarker for breast cancer treatment. 

Retracted: Yes

PubPeer comments:
 This article has been retracted: https: pubs.rsc.org en content articlelanding 2019 RA C8RA06750C#!divAbstract The manuscript should never have been consideres in a serious journal. A quick look at the artificial Western immunoblots should be enough, in addition to a nonsense email address. ,