PReD-Bench/PRed-Bench huggingface dataset:
Circular RNA hsa_circ_0055538 regulates the malignant biological behavior of oral squamous cell carcinoma through the p53/Bcl-2/caspase signaling pathway
Authors: Shuai Sun
Hongyu Yang
Wen Su
Yuehong Shen
Feng Wang
Journal: Journal of Translational Medicine (2019)
Discipline: CLINICAL MEDICINE
Keywords: Circular RNA; Oral tumor; Squamous cell carcinoma; p53/Bcl-2/caspase signaling pathway.
Affiliations: Clinical School, Peking University Shenzhen Hospital, Anhui Medical University, Shenzhen, 518036, Guangdong, China., Department of Oral and Maxillofacial Surgery, Peking University Shenzhen Hospital, No. 1120 Lianhua Road, Shenzhen, 518036, Guangdong, China., Clinical School, Peking University Shenzhen Hospital, Anhui Medical University, Shenzhen, 518036, Guangdong, China. ., Department of Oral and Maxillofacial Surgery, Peking University Shenzhen Hospital, No. 1120 Lianhua Road, Shenzhen, 518036, Guangdong, China. .

Abstract:  Background: Oral squamous cell carcinoma (OSCC) is a common oral and maxillofacial malignant tumor with high rates of metastasis and mortality. Circular RNAs (circRNAs), a type of non-coding RNA, are involved in the development of a variety of tumors. The roles of circRNAs in OSCC are unclear; in this study, the correlation between the circRNA hsa_circ_0055538, previously identified by high-throughput sequencing, and the biological behavior of OSCC was evaluated. Methods: circRNA expression was evaluated using patient tissue samples and various OSCC cell lines. The effects of overexpression and knockdown were evaluated by lentiviral infection and siRNA transfection of the SCC9 and CAL27 cell lines. Migration, invasion, apoptosis, and the expression of proteins in the p53 signaling pathway were evaluated. Infected cells were injected into nude mice to evaluate tumorigenesis. Results: Low hsa_circ_0055538 expression levels were verified in tumor tissues and OSCC cell lines. Clinical data analysis showed that the expression level is related to the degree of tumor differentiation. Lentiviral infection and siRNA transfection of SCC9 and CAL27 cell lines revealed that changes in circRNA expression significantly affected the malignant biological behavior of OSCC cells. Importantly, nude mouse experiments showed that high expression of hsa_circ_0055538 inhibited tumor growth. Finally, hsa_circ_0055538 may affect the development of OSCC via the p53/Bcl-2/caspase signaling pathway. Conclusions: Our results indicated that hsa_circ_0055538 is involved in OSCC via the p53 signaling pathway and may be a diagnostic and/or prognostic marker as well as a therapeutic target. 

Retracted: No

PubPeer comments:
 FIGURE 1D seems that the picture is duplicated![file] ,
Highly active multiple sclerosis: An update
Authors: Diego M Rivera
Luis Alfonso Zarco
Cindy Díaz
Journal: Multiple sclerosis and related disorders (2019)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: Highly active multiple sclerosis; Multiple sclerosis; Review.
Affiliations: Neurological Resident. Department of Neurology, Hospital Universitario San Ignacio, Universidad Javeriana, Bogotá, Colombia. Electronic address: ., Neuroimmunologist, Director of the Neurology Service, Hospital Universitario San Ignacio, Universidad Javeriana, Bogotá, Colombia., Neuroradiológo, Hospital Universitario San Ignacio; Universidad Pontifica Javeriana, Bogotá, Colombia.

Abstract:  Multiple sclerosis (MS) is the most prevalent chronic inflammatory disease of the central nervous system (CNS), affecting more than 2 million people worldwide. It is characterized by brain and spinal cord involvement. There are the relapsing remitting MS (RRMS), primary progressive MS (PPMS), and secondary progressive MS (SPMS) phenotypes. There is a subgroup of RRMS patients who have a more aggressive disease course marked by a rapid accumulation of physical and cognitive deficit, despite treatment with 1 or more disease modifying drugs (DMTs). In the past, this disease phenotype was called "aggressive" MS (AMS); it is now called highly active MS (HAMS). It is generally agreed that the severe nature of this phenotype requires different treatment decisions. Unfortunately, there is no consensus on the definition of AMS or the treatment algorithm. In this article we review HAMS in relation to its definition and the treatments available. 

Retracted: No

PubPeer comments:
 This review shows concerning verbatim reproductions from the sources cited. These issues were informed to the editorial committee, and were not deemed of sufficient concern. , 
 We read with great concern this paper from Du00edaz et al, due to striking similarities with an earlier review in some aspects of its content. There are some ideas written exactly as in Rush et al. 2015 (doi:10.1038 nrneurol.2015.85), of which some snapshots are shown below. We performed an atomated analysis which can be found in the following link: https: copyleaks.com dashboard v1 businesses report t6cmcij0sb6aw626 preview?key=4dzqq1buycxnz5pq suspectId=4ebe36cbd8 viewMode=one-to-one contentMode=html sourcePage=1 suspectPage=1 Althoug we know this is an area without a great deal of evidence, we feel that the similarities are unjustifiable. We hope that this observations are worthy of a pubpeer comment. ![file] ![file] ![file] , 
 This article has a great similarity with this article published in Nature Reviews Neurology. See the text, the tables, and algorithm. The text was paraphrased. Rush, C., MacLean, H. Freedman, M. Aggressive multiple sclerosis: proposed definition and treatment algorithm. Nat Rev Neurol 11, 379u2013389 (2015). https: doi.org 10.1038 nrneurol.2015.85 ,
Decoy receptor 3 overexpression and immunologic tolerance in hepatocellular carcinoma (HCC) development
Authors: Juan Wang
Pinh Yin
Guohong Zhuang
Caixia Chen
Changgong Zhang
Jinhua Su
Hongfang Luo
Journal: Cancer Investigation (2008)
Discipline: CLINICAL MEDICINE
Keywords: DcR3; FasL; apoptosis; immune escape system; neoplastic cells
Affiliations: Anti-Cancer Research Center, Xiamen University Medical College, XiaMen, China.

Abstract:  The recently identified decoy receptor 3 (DcR3) inhibits FasL-induced apoptosis by binding to FasL, and it is considered to play a key role in the immune escape system of neoplastic cells. In order to examine the involvement of DcR3 in the immunologic tolerance of hepatocellular carcinoma (HCC), we investigated the amplification and expression of DcR3, FasL, and Fas in an HCC mice model using RT-PCR, western blotting, and ELISA, and analyzed the space-time relationship with various cytokines including the forkhead transcription factor forkhead/winged helix transcription factor gene (Foxp3), CTLA-4, TGF-beta, IL-10, TNF-alpha, and IFN-gamma. The RT-PCR results revealed that Fas expression preceded that of DcR3 during the early phases of tumorigenesis. Thereafter, the expression of DcR3 was up-regulated; however, the expression of Fas was down-regulated and eventually ceased. DcR3 and FasL were expressed and amplified simultaneously in muscle tumor. CTLA-4 expression was earlier than Foxp3, and both CTLA-4 and Foxp3 amplification and expression were consistent with that of DcR3. The results suggest that the elevated levels of DcR3, Foxp3, and CTLA-4 in tissue were positively correlated with tumor growth. The partial tumor immunoregulation inclined to negative modulation, and DcR3 may play an important role in inducing immunologic tolerance. 

Retracted: No

PubPeer comments:
 Several concerns about Figures 1, 3, and 4, reported to the journal in 2015. * Boxes of the same color highlight lanes or panels that look similar to each other, although they represent different genes or anatomical sites. ![file] ,
Translational regulation of the mRNA encoding the ubiquitin peptidase USP1 involved in the DNA damage response as a determinant of Cisplatin resistance
Authors: Carole Helissey
Ken A Olaussen
Céline Lefebvre
Jean-Charles Soria
Tony Sourisseau
Hélène Malka-Mahieu
Stephan Vagner
Florence Ponsonnailles
Fabrice André
Journal: Cell Cycle (2016)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: 5′ untranslated region; cisplatin resistance; deubiquitination; lung cancer; monoubiquitination
Affiliations: Inserm Unit 981, DHU TORINO; Gustave Roussy and University Paris Sud; Villejuif, France, Institut Curie; Center de Recherche; Orsay, France, CNRS UMR3348; Orsay, France, University Paris-Sud XI; Orsay, France, PSL research university; Paris, France

Abstract:  Cisplatin (cis-diaminedichloroplatin (II), CDDP) is part of the standard therapy for a number of solid tumors including Non-Small-Cell Lung Cancer (NSCLC). The initial response observed is in most cases only transient and tumors quickly become refractory to the drug. Tumor cell resistance to CDDP relies on multiple mechanisms, some of which still remain unknown. In search for such mechanisms, we examined the impact of CDDP on mRNA translation in a sensitive and in a matched resistant NSCLC cell line. We identified a set of genes whose mRNAs are differentially translated in CDDP resistant vs. sensitive cells. The translation of the mRNA encoding the Ubiquitin-Specific Peptidase 1 (USP1), a Ubiquitin peptidase with important function in multiple DNA repair pathways, is inhibited by CDDP exposure in the sensitive cells, but not in the resistant cells. This lack of down-regulation of USP1 expression at the translational level plays a primary role in CDDP resistance since inhibition of USP1 expression or activity by siRNA or the small molecule inhibitor ML323, respectively is sufficient to re-sensitize resistant cells to CDDP. We involved the USP1 mRNA translation as a major mechanism of CDDP resistance in NSCLC cells and suggest that USP1 could be evaluated as a candidate predictive marker and as a therapeutic target to overcome CDDP resistance. More generally, our results indicate that analysis of gene expression at the level of mRNA translation is a useful approach to identify new determinants of CDDP resistance. 

Retracted: No

PubPeer comments:
 Could the authors comment on what appear to be some repeated features? ![file] ,
Inhibition of Ep3 attenuates migration and promotes apoptosis of non‑small cell lung cancer cells via suppression of TGF‑β/Smad signaling
Authors: Lei Li
Dengfeng Yan
Yanping Lv
Journal: Oncology Letters (2018)
Discipline: CLINICAL MEDICINE
Keywords: E-prostanoid 3; cell growth; cell invasion; non-small cell lung cancer cells; tumor growth factor-β/Smad signaling.
Affiliations: Department of Respiration, Zhoukou Central Hospital, Zhoukou, Henan 466000, P.R. China.

Abstract:  Non-small cell lung cancer (NSCLC) is the most common cause of cancer-associated mortality worldwide. Prostaglandin E2 (PGE2) regulates various biological processes, including invasion, proliferation and apoptosis. E-prostanoid 3 (Ep3) is a PGE2 receptor, and the functional role of Ep3 in the progression of NSCLC remains unresolved. The present study investigated the effects of Ep3 in A549 cells and explored the underlying molecular mechanisms. The results revealed that the mRNA and protein expression levels of Ep3 were significantly upregulated in NSCLC tissues and A549 cells. Pharmacological inhibition of Ep3 or RNA interference against Ep3 attenuated the cell viability, migration and invasion, and promoted apoptosis in A549 cells. Ep3 deficiency also decreased the expression of transforming growth factor (TGF)-β, phosphorylated (p)-Smad2 and p-Smad3. The transfection of TGF-β overexpression plasmids reversed the effects of Ep3 deficiency on the cell viability and apoptosis in A549 cells. Finally, an in vivo experiment revealed that Ep3-siRNA transfection strongly reduced the tumor growth and tumor volume. The Ep3-siRNA transfection also inhibited tumor metastasis via suppression of the expression of metastasis-associated proteins. Taken together, these findings indicate that inhibition of Ep3 attenuates the viability and migration, and promotes the apoptosis of NSCLC through suppression of the TGF-β/Smad signaling pathway. Targeting of the Ep3/TGF-β/Smad signaling pathway may be a novel therapeutic strategy for the prevention and treatment of NSCLC. 

Retracted: No

PubPeer comments:
 Fig 6A:  A NSCLC xenograft mouse model was created by subcutaneous injection of A549 cells transfected with or without Ep3 siRNA to SPF nude mice. (A) Representative tumors from two groups mice are presented . ![] One of a [series of images] depicting mouse xenograft tumors presented on the same fabric bench cover, with the same ruler for scale, from otherwise-unrelated laboratories. Often the same tumors. Here, Fig 8A from [Fan et al (2017)] . ![] ,
The Drosophila cohesin subunit Rad21 is a trithorax group (trxG) protein
Authors: Scott L Page
Samantha A Beck
Dale Dorsett
Graham Hallson
Hugh W Brock
William D Warren
Donald A R Sinclair
James A Kennison
Monika Syrzycka
Barry M Honda
Rebecca Keall
Sally M Hunter
Journal: Proceedings of the National Academy of Sciences of the United States of America (2008)
Discipline: Multidisciplinary
Keywords: cohesin complex; cell division; sister chromatid cohesion; transcription regulation; chromatin immunoprecipitation
Affiliations: Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC, Canada V5A 1S6.

Abstract:  The cohesin complex is a key player in regulating cell division. Cohesin proteins SMC1, SMC3, Rad21, and stromalin (SA), along with associated proteins Nipped-B, Pds5, and EcoI, maintain sister chromatid cohesion before segregation to daughter cells during anaphase. Recent chromatin immunoprecipitation (ChIP) data reveal extensive overlap of Nipped-B and cohesin components with RNA polymerase II binding at active genes in Drosophila. These and other data strongly suggest a role for cohesion in transcription; however, there is no clear evidence for any specific mechanisms by which cohesin and associated proteins regulate transcription. We report here a link between cohesin components and trithorax group (trxG) function, thus implicating these proteins in transcription activation and/or elongation. We show that the Drosophila Rad21 protein is encoded by verthandi (vtd), a member of the trxG gene family that is also involved in regulating the hedgehog (hh) gene. In addition, mutations in the associated protein Nipped-B show similar trxG activity i.e., like vtd, they act as dominant suppressors of Pc and hh(Mrt) without impairing cell division. Our results provide a framework to further investigate how cohesin and associated components might regulate transcription. 

Retracted: No

PubPeer comments:
 Concerns about Figures 5, 7, and 8. Reported to the journal in 2015. Unexpected similarities between b-actin panels representing different treatments (FGF vs PDGF) on cells. Shown with blue and red boxes. ![file] ,
MiR-411-5p acts as a tumor suppressor in non-small cell lung cancer through targeting PUM1
Authors: Q-D Sun
L-H Xia
Q-H Yan
Y-P Gao
Journal: European review for medical and pharmacological sciences (2018)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: miR-411-5p; non-small cell lung cancer; PUM1; biological behavior; molecular mechanism
Affiliations: Endoscopy Center, Linyi Central Hospital, Linyi, China. .

Abstract:  Objective: The aim of this study was to investigate the expression of micro ribonucleic acid-411-5P (miR-411-5p) in non-small cell lung cancer (NSCLC), and to explore the effect of miR-411-5p on the biological behavior of NSCLC cells as well as the underlying molecular mechanism. Patients and methods: Quantitative Real Time- Polymerase Chain Reaction (qRT-PCR) was used to detect the expression level of miR-411-5p in NSCLC tissues and cells. MiR-411-5p mimics and relevant controls were transfected into NSCLC cells according to the instructions of Lipidosome 2000. Transfected cells were divided into the experimental group and the control group. The transfection efficiency of each group was detected by qRT-PCR. After miR-411-5p overexpression, methyl thiazolyl tetrazolium (MTT) assay, flow cytometry, and transwell assay were used to detect the biological changes of cells in each group. Bioinformatics predicted that pumilio homolog 1 (PUM1) was the target gene of miR-411-5p. Subsequently, the mRNA and protein expression level of PUM1 in each group was detected by qRT-PCR and Western blotting, respectively. Dual-luciferase reporter assay was used to validate the target regulatory relationship between miR-411-5p and PUM1. Results: The results of qRT-PCR showed that miR-411-5p was relatively lowly expressed in NSCLC tissues and cells. After miR-411-5p overexpression, MTT results revealed that the proliferation of NSCLC cells was decreased. Flow cytometry results indicated that the apoptosis rate of NSCLC cells was increased, and cell cycle was arrested in the G0-G1 phase. Meanwhile, the transwell assay demonstrated that the migration and invasion abilities of NSCLC cells were decreased. Bioinformatics predicted that PUM1 was the target gene of miR-411-5p. After miR-411-4p was overexpressed in NSCLC cells, qRT-PCR and Western blotting showed that both the mRNA and protein expression levels of PUM1 were up-regulated. Moreover, dual-luciferase reporter assay demonstrated that miR-411-5p could significantly inhibit the luciferase activity of wild-type PUM1-3'-untranslated region (3'-UTR). However, it exhibited no effect on the luciferase activity of cells transfected with mutant plasmids. Conclusions: MiR-411-5p may be involved in regulating the biological function of NSCLC cells via targeting PUM1. In addition, miR-411-5p may serve as a potential target for the molecular therapy of NSCLC. 

Retracted: No

PubPeer comments:
 Figure 3C: Two panels appear to show an area of overlap. ![file] ,
Protective effect of DNA vaccine encoding pseudomonas exotoxin A and PcrV against acute pulmonary P. aeruginosa Infection
Authors: Mingzi Jiang
Jing Yao
Ganzhu Feng
Journal: PLoS ONE (2014)
Discipline: Multidisciplinary
Keywords: Pseudomonas aeruginosa; DNA vaccine; immunotherapy; Exotoxin A; tip protein
Affiliations: Department of Respiratory, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.

Abstract:  Infections with Pseudomonas aeruginosa have been a long-standing challenge for clinical therapy because of complex pathogenesis and resistance to antibiotics, thus attaching importance to explore effective vaccines for prevention and treatment. In the present study, we constructed a novel DNA vaccine by inserting mutated gene toxAm encoding Pseudomonas Exotoxin A and gene pcrV encoding tip protein of the type III secretion system into respective sites of a eukaryotic plasmid pIRES, named pIRES-toxAm-pcrV, and next evaluated the efficacy of the vaccine in murine acute Pseudomonas pneumonia models. Compared to DNA vaccines encoding single antigen, mice vaccinated with pIRES-toxAm-pcrV elicited higher levels of antigen-specific serum immunoglobulin G (IgG), enhanced splenic cell proliferation and cytokine secretion in response to Pseudomonas aeruginosa antigens, additionally PAO1 challenge in mice airway resulted in reduced bacteria burden and milder pathologic changes in lungs. Besides, it was observed that immunogenicity and protection could be promoted by the CpG ODN 1826 adjuvant. Taken together, it's revealed that recombinant DNA vaccine pIRES-toxAm-pcrV was a potential candidate for immunotherapy of Pseudomonas aeruginosa infection and the CpG ODN 1826 a potent stimulatory adjuvant for DNA vaccination. 

Retracted: No

PubPeer comments:
 Figure 5A. Reported to the journal in 2015. * Green boxes: the pcrV and toxAm-pcrV panels appear to show an overlap. ![file] ,
Long noncoding RNA DSCAM-AS1 functions as an oncogene in non-small cell lung cancer by targeting BCL11A
Authors: N Xie
J Liao
Journal: European review for medical and pharmacological sciences (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: lncRNAs; DSCAM-AS1; non-small cell lung cancer (NSCLC); tumor progression; overall survival rate
Affiliations: Department of Thoracic Surgery, Yantaishan Hospital, Yantai, China. .

Abstract:  Objective: Long noncoding RNAs (lncRNAs) have attracted more attention for their role in tumor progression recently. The aim of this study was to investigate the role of DSCAM-AS1 in the progression of non-small cell lung cancer (NSCLC), and to elucidate its possible underlying mechanism. Patients and methods: DSCAM-AS1 expression in both NSCLC cells and tissue samples was detected by Real Time quantitative-Polymerase Chain Reaction (RT-qPCR). Moreover, the association between the DSCAM-AS1 expression level and patients' overall survival rate was explored. Furthermore, wound healing assay and transwell assay were conducted. In addition, RT-qPCR and Western blot assay were used to elucidate the underlying mechanism. Results: DSCAM-AS1 expression level in NSCLC samples was significantly higher than that of the corresponding normal tissues. The expression level of DSCAM-AS1 was associated with an overall survival time of NSCLC patients. Besides, the migration and invasion abilities of NSCLC cells were remarkably promoted after DSCAM-AS1 overexpression in vitro. Moreover, the mRNA and protein expression of BCL11A was significantly upregulated after the overexpression of DSCAM-AS1. Furthermore, the expression of BCL11A was positively correlated with DSCAM-AS1 expression in NSCLC tissues. Conclusions: We observed that DSCAM-AS1 could enhance NSCLC cell migration and invasion via upregulating BCL11A. Furthermore, DSCAM-AS1 might be a potential therapeutic target for NSCLC. 

Retracted: No

PubPeer comments:
 Fig 5. ![file] The Western Blots in this paper have a stylised appearance, characteristic of products of the  Tadpole papermill . ,
MiR-20a regulates fibroblast-like synoviocyte proliferation and apoptosis in rheumatoid arthritis
Authors: C-X Lu
W-Z Lu
S-B Wei
Z-X Long
J-L Lu
J-Q Liang
X-J Wei
X-W Li
Journal: European review for medical and pharmacological sciences (2020)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: research misconduct; MiR-20a; fibroblast-like synoviocyte; proliferation; apoptosis
Affiliations: Department of Orthopedics, Baise People's Hospital, Baise, Guangxi Province, China.

Abstract:  Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "MiR-20a regulates fibroblast-like synoviocyte proliferation and apoptosis in rheumatoid arthritis, by X.-J. Wei, X.-W. Li, J.-L. Lu, Z.-X. Long, J.-Q. Liang, S.-B. Wei, C.-X. Lu, W.-Z. Lu, published in Eur Rev Med Pharmacol Sci 2017; 21 (17): 3886-3893-PMID: 28975975" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/13351. 

Retracted: No

PubPeer comments:
 Retraction withdrawal notice for [ MiR-20a regulates fibroblast-like synoviocyte proliferation and apoptosis in rheumatoid arthritis ] - not worth commenting on in its own right, but too late now. , 
 #1 An August 19, 2021 [announcement ](http: www.nhc.gov.cn cms-search xxgk getManuscriptXxgk.htm?id=159bcc53148340d48336060e65571a1c) by  National Health Commission of the People s Republic of China reported the results of investigation of 10 papers flagged on Pubpeer, together with disciplinary actions against the authors. The current paper is the #8 case in the list and the investigation concluded that this paper was purchased from a papermill. Here is a screenshot: ![file] ,
MicroRNA-130b promotes cell proliferation and invasion by inhibiting peroxisome proliferator-activated receptor-γ in human glioma cells
Authors: Hong-Jie Chen
Jian-He Zhang
Shou-Sen Wang
Jian-Jun Gu
Journal: International Journal of Molecular Medicine (2016)
Discipline: CLINICAL MEDICINE
Keywords: MicroRNA-130b; tumorigenesis; gliomas; RT-qPCR; expression levels
Affiliations: Department of Neurosurgery, Fuzhou General Hospital, Xiamen University Medical College, Fuzhou, Fujian 350025, P.R. China.

Abstract:  MicroRNA-130b (miR-130b) is a novel tumor-related miRNA that has been found to be involved in several biological processes. However, there is limited evidence regarding the role of miR-130b in the tumorigenesis of human gliomas. In the present study, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) assays were used to quantify miR-130b expression levels in human glioma tissues and glioma cell lines (U251, U87, SNB19 and LN229). The expression level of miR-130b was found to be markedly higher in human glioma tissues than in non‑neoplastic brain specimens. Specifically, higher expression levels of miR‑130b were observed in the glioma cell lines, compared with those in normal human astrocytes (NHA). We also confirmed that miR‑130b interacted with the 3'-untranslated region of peroxisome proliferator‑activated receptor-γ (PPAR‑γ), which negatively affected the protein levels of E-cadherin. Furthermore, its effects on cell proliferation and invasion were examined using CCK8, colony formation, cell cycle and Transwell assays. We found that the upregulation of miR-130b induced cell proliferation, decreased the percentage of cells in the G0/G1 phase and enhanced the invasiveness of U251 glioma cells whereas the downregulation of miR-130b exerted opposing effects. Moreover, it was demonstrated that the downregulation of miR‑130b in U251 glioma cells restored the expression of PPAR-γ and E-cadherin, and inhibited the expression of β-catenin. Notably, PPAR-γ knockdown abolished the inhibitory effect of miR-130b inhibitor on the proliferation and invasivness of U251 cells. Taken together, these findings suggest that miR‑130b promotes the proliferation and invasion of U251 glioma cells by inhibiting PPAR-γ. 

Retracted: No

PubPeer comments:
null, 
 #1 Much of  Unregistered Submission s contribution was evidently lost in the Great Migration to PubPeer 2.0. Here I stretched Figs 5A and 6B by 200% horizontally, because the original compression made it hard to focus on the details. A few repeated elements are marked. ![file] The two NC panels are clearly very similar. Here I have color-reversed 6B NC and superimposed it upon 5A NC, so that identical regions of the images simply cancel out. ![file] In the same way, here is an overlay of the 5A mimic and 6B inhibitor+ panels, which are also very similar. ![file] , 
 Fig 5B is also a source of alarm. ![file] A few repeating motifs from one panel: ![file] Some from the 24-hour Inhibitor panel ![file] The two Mimic panels superimposed (after color-reversing the 24-hour version). ![file] ,
Gefitinib (Iressa) represses FOXM1 expression via FOXO3a in breast cancer
Authors: Richard E Francis
Stephanie K Guest
Barrie Peck
Ursula B McGovern
Stephen S Myatt
Jimmy M-M Kwok
Janna Krol
R Charles Coombes
Jun Wang
Eric W-F Lam
Andreas Polychronis
Journal: Molecular Cancer Therapeutics (2009)
Discipline: CLINICAL MEDICINE
Keywords: Gefitinib; epidermal growth factor receptor inhibitor; FOXM1; breast cancer; resistance
Affiliations: Cancer Research UK Labs, Department of Oncology, Imperial College London, MRC Cyclotron Building, Imperial College School of Medicine at Hammersmith Hospital, Du Cane Road, London W12 0NN, United Kingdom.

Abstract:  Gefitinib (Iressa) is a specific and effective epidermal growth factor receptor inhibitor. An understanding of the downstream cellular targets of gefitinib will allow the discovery of biomarkers for predicting outcomes and monitoring anti-epidermal growth factor receptor therapies and provide information for overcoming gefitinib resistance. In this study, we investigated the role and regulation of FOXM1 in response to gefitinib treatment in breast cancer. Using the gefitinib-sensitive breast carcinoma cell lines BT474 and SKBR3 as well as the resistant lines MCF-7, MDA-MB-231, and MDA-MB-453, we showed that gefitinib represses the expression of the transcription factor FOXM1 in sensitive, but not resistant, cells. FOXM1 repression by gefitinib is associated with FOXO3a activation and is mediated at the transcriptional level and gene promoter level. These results were verified by immunohistochemical staining of biopsy samples from primary breast cancer patients obtained from a gefitinib neoadjuvant study. We also showed that ectopic expression of an active FOXO3a represses FOXM1 expression, whereas knockdown of FOXO3a expression using small interfering RNA can up-regulate FOXM1 and its downstream targets polo-like kinase, cyclin B1, and CDC25B and rescue sensitive BT474 cells from gefitinib-induced cell proliferative arrest. These results suggest that gefitinib represses FOXM1 expression via FOXO3a in breast cancer. We further showed that overexpression of a wild-type FOXM1 or a constitutively active FOXM1, DeltaN-FOXM1, abrogates the cell death induced by gefitinib, indicating that FOXM1 has a functional role in mediating the gefitinib-induced proliferative arrest and in determining sensitivity to gefitinib. In summary, our study defined FOXM1 as a cellular target and marker of gefitinib activity in breast cancer. 

Retracted: No

PubPeer comments:
 ![file] , 
 Figure 2A Mol Cancer Ther 6,3169. SKBR3 p27kip1 and Bim panels do not look like they come from the same blot. , 
 Figure 2 ( this paper) much more similar than expected. ![file] , 
 Figure 2 (this paper) leftmost 4 actin panels much more similar than expected, yet leftmost 4 EGFR and leftmost 4 Total FOXO3a panels different. ![file] , 
 https: retractionwatch.com 2021 05 28 imperial-college-london-researcher-fired-for-research-misconduct ,
Bmi-1 is a novel molecular marker of nasopharyngeal carcinoma progression and immortalizes primary human nasopharyngeal epithelial cells
Authors: Goberdhan P Dimri
Vimla Band
Mu-Sheng Zeng
Qiu-Liang Wu
Ling Zhang
Jian-Yong Shao
Li-Wu Fu
Yun-Fei Xia
Hao-Yuan Mo
Man-Zhi Li
Wan-Li Liu
Li-Bing Song
Wen-Ting Liao
Wen-Lin Huang
Yi-Xin Zeng
Journal: Cancer Research (2006)
Discipline: CLINICAL MEDICINE
Keywords: Bmi-1; proliferation; oncogenesis; senescence; immortalization
Affiliations: State Key Laboratory of Oncology in Southern China, Sun Yat-sen University Cancer Center, Guangzhou, China.

Abstract:  The Bmi-1 oncoprotein regulates proliferation and oncogenesis in human cells. Its overexpression leads to senescence bypass in human fibroblasts and immortalization of human mammary epithelial cells. In this study, we report that compared with normal nasopharyngeal epithelial cells (NPEC), Bmi-1 is overexpressed in nasopharyngeal carcinoma cell lines. Importantly, Bmi-1 was also found to be overexpressed in 29 of 75 nasopharyngeal carcinoma tumors (38.7%) by immunohistochemical analysis. In contrast to nasopharyngeal carcinoma, there was no detectable expression of Bmi-1 in noncancerous nasopharyngeal epithelium. Moreover, high Bmi-1 expression positively correlated with poor prognosis of nasopharyngeal carcinoma patients. We also report that the overexpression of Bmi-1 leads to bypass of senescence and immortalization of NPECs, which normally express p16(INK4a) and exhibit finite replicative life span. Overexpression of Bmi-1 in NPECs led to the induction of human telomerase reverse transcriptase activity and reduction of p16(INK4a) expression. Mutational analysis of Bmi-1 showed that both RING finger and helix-turn-helix domains of it are required for immortalization of NPECs. Our findings suggest that Bmi-1 plays an important role in the development and progression of nasopharyngeal carcinoma, and that Bmi-1 is a valuable marker for assessing the prognosis of nasopharyngeal carcinoma patients. Furthermore, this study provides the first cellular proto-oncogene immortalized nasopharyngeal epithelial cell line, which may serve as a cell model system for studying the mechanisms involved in the tumorigenesis of nasopharyngeal carcinoma. 

Retracted: No

PubPeer comments:
 Fig. 5C and Fig. 7B. Two WB bands appear more similar than expected. ![file] ,
Loss of MicroRNA-489-3p promotes osteosarcoma metastasis by activating PAX3-MET pathway
Authors: Qifei Liu
Guochun Yang
Yuying Qian
Journal: Molecular carcinogenesis (2017)
Discipline: CLINICAL MEDICINE
Keywords: MET; MicroRNA-489-3p; PAX3; metastasis; osteosarcoma.
Affiliations: Department of Emergency, Affiliated Hospital of Shandong Academy of Medical Sciences, Jinan, China., Department of Nephrology, Affiliated Hospital of Shandong Academy of Medical Sciences, Jinan, China.

Abstract:  Osteosarcoma (OS) remains one deadly disease for many affected patients. MicroRNAs (miRNAs) are thought to have an important role in tumor metastasis by regulating diverse cellular pathways. Here, we describe the function and regulation network of miR-489-3p in osteosarcoma (OS) metastasis. MiR-489-3p expression was downregulated in OS cells especially in high metastatic potential cells and was also significantly decreased in metastatic lesions compared with their corresponding primary tumor samples. Both gain- and loss-of-function studies confirmed that miR-489-3p significantly suppressed OS cell invasion and metastasis both in vitro and in vivo. Mechanistically, paired box gene 3 (PAX3) was identified as a functional target of miR-489-3p in OS cells. MiR-489-3p inhibited OS metastasis by negatively regulating expression of PAX3. In addition, PAX3 expression was markedly higher in OS tissues than in adjacent non-cancerous tissues. Transwell assays and in vivo metastasis assays demonstrated that overexpression of PAX3 significantly promoted the invasiveness and pulmonary metastasis of OS cells. On the other hand, downregulation of PAX3 markedly reduced cell metastatic potential. Mechanistic investigations indicated that prometastasis function of PAX3 was mediated by upregulating downstream target MET tyrosine kinase receptor. In conclusion, our results reveal that miR-489-3p-PAX3-MET signaling is critical to OS metastasis. Targeting the pathway described here may open new therapeutic prospects to restrict the metastatic potential of OS. © 2016 Wiley Periodicals, Inc. 

Retracted: No

PubPeer comments:
  Figure 5. PAX3 regulated MET. ... (D) Immunofluorescence staining of PAX3 and MET in OS cells when transfected with PAX3-expression lentiviral vectors or PAX3 siRNA vectors. ![file] Labels on the rows do not match the figure Legend. Two panels are unlikely to have come from separate samples. ,
Functional characterization of hepatocyte nuclear factor-4 alpha dimerization interface mutants
Authors: Eleni Aggelidou
Olga Piltsi
Constantinos Demetriades
Margarita Hadzopoulou-Cladaras
Panagiota Iordanidou
Journal: FEBS Journal (2006)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: HNF-4alpha; dimerization; DNA binding; protein stability; ligand binding
Affiliations: Department of Genetics, Development and Molecular Biology, Laboratory of Developmental Biology, School of Biology, Aristotle University of Thessaloniki, Greece.

Abstract:  Hepatocyte nuclear factor-4 (HNF-4alpha), a member of the nuclear receptor superfamily, binds DNA exclusively as a homodimer. Dimerization controls important aspects of receptor function, such as DNA binding, protein stability, ligand binding and interaction with coactivators. Crystallographic data of the HNF-4alpha ligand-binding domain (LBD) demonstrated that the homodimer interface is composed of residues in helices 7, 9 and 10 with intermolecular salt bridges, hydrogen bonds and hydrophobic interactions contributing to the stability of the interface. To investigate the importance of the proposed ionic interactions for HNF-4alpha dimerization, interactions critical for formation of the LBD homodimer interface were disrupted by introducing point mutations in residues D261N (H7), E269Q (H7), Q307L (H9), D312N (H9) and Q336L (H10). Mutants were analysed for transactivation, coactivator interaction, DNA binding and dimerization. EMSA analysis showed that the mutants are able to bind DNA as dimers and coimmunoprecipitation assays confirmed dimerization in solution. Furthermore, the mutations do not compromise HNF-4alpha activity and are responsive to PPAR-gamma coactivator-1 (PGC-1). Finally, residue R324, located in the H9/H10 loop, which was suspected to be involved in dimer stabilization via an ionic interaction with residue E276, was studied. In contrast to the conservative substitution R324H the mutation R324L abolishes HNF-4alpha transcriptional activity and coactivator recruitment, revealing that the nature of substitution may play an important role in HNF-4alpha function. 

Retracted: No

PubPeer comments:
 Fig. 2A from this paper seems very similar to Fig. 5A of Iordanidou et al., 2005 (doi: 10.1074 jbc.M501221200) ![file] , 
 Thank you for bringing this to our attention. We have indeed used the wrong image during the preparation of this panel. We apologize for this unintentional mistake and we have already contacted the journal to issue a correction. Although these data were generated more than 15 years ago, we looked back at our records and identified the correct original raw data. For clarity reasons, we also provide here the corrected Figure panel as well as the respective uncropped film. In the new version, a dashed line indicates a cropped lane that contains an irrelevant sample. We would like to note that these changes do not affect any of the original conclusions. ![file] ,
Regulation of adiponectin in adipocytes upon exposure to HIV-1
Authors: G Tan
G S Hotamisligil
C M Hadigan
P J Kanki
S K Grinspoon
Q Tong
J-L G Sankalé
Journal: HIV Medicine (2006)
Discipline: IMMUNOLOGY
Keywords: Adipose dysregulation; dyslipidemia; insulin resistance; HIV-related lipodystrophy; adiponectin
Affiliations: Department of Immunology & Infectious Diseases and Harvard AIDS Institute, Harvard School of Public Health, Boston, MA, USA.

Abstract:  Objectives: Adipose dysregulation, dyslipidemia, and insulin resistance are hallmarks of HIV-related lipodystrophy. The precise mechanisms behind these disturbances are unknown. In HIV-infected patients, we previously demonstrated a strong relationship between lipodystrophy and levels of adiponectin, an adipose peptide implicated in regulation of glucose and lipid metabolisms. In this study we investigated the effect of HIV on adipocytes, to determine whether HIV can directly infect adipocytes and/or alter the regulation and secretion of the adipocyte-derived hormone adiponectin. Methods: Human subcutaneous preadipocytes and adipocytes were exposed to HIV-1 under various conditions. Adiponectin was measured in supernatants and cell lysates. Results: Although adipocytes expressed CD4, the major HIV receptor, they could not be infected in vitro. However, exposure to HIV dramatically increased the secretion of adiponectin from human adipocytes, in the absence of infection. This was exacerbated with sustained exposure to HIV in a transwell assay. Further, human peripheral mononuclear cells also produced adiponectin, but this was largely dependent upon T-cell activation. Conclusions: We propose that the stimulation of adiponectin production by HIV can perturb adiponectin regulation, leading to substantially decreased levels upon viral suppression by antiretroviral therapy. These data suggest a potential molecular mechanism of adiponectin regulation in HIV-infected patients. 

Retracted: No

PubPeer comments:
 Fig. 1a u2013 More similar than expected. Could authors check it please? ![file] ,
Germinal center B cells are dispensable in prion transport and neuroinvasion
Authors: Burkhard Becher
Christian Federau
Mareike Wagner
Johannes Haybaeck
Lotta von Boehmer
Adriano Aguzzi
Nicolas Zeller
Mathias Heikenwalder
Marco Prinz
Petra Schwarz
Journal: Journal of neuroimmunology (2007)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: Transmissible spongiform encephalopathies; prion replication; lymphoreticular system; CD40; germinal center B cells
Affiliations: Institute of Neuropathology, University Hospital of Zurich, Schmelzbergstrasse 12, CH-8091 Zurich, Switzerland.

Abstract:  Transmissible spongiform encephalopathies (TSEs) are fatal neurodegenerative diseases of animals and humans. Many TSEs are initiated by prion replication in the lymphoreticular system (LRS). The cellular and molecular prerequisites for prion trafficking within the LRS are not fully understood. Here we have manipulated CD40 and its ligand to investigate whether genetic or pharmacological ablation of germinal center B cells (GCBs), which migrate into and out of germinal centers, influences prion pathogenesis. In contrast to previous reports, no alteration of prion pathogenesis was detected in mice lacking CD40L and in mice treated with anti-CD40L antibodies. These results suggest that GCBs alone do not impact peripheral splenic prion transport, replication efficiency, or neuroinvasion, and point to other mechanisms affecting prion transport from lymphoreticular sites of replication to the nervous system. 

Retracted: No

PubPeer comments:
 Figure 4C. * Red boxes: In the Iba-1 column, the low dose Ha-IgG treatment panel and the Mr-1 treatment panel appear to look identical. Could the authors please check? ![file] , 
 Thank you for pointing out a possible problem. I agree with your concern and I will try to retrieve the original histology slides. I cannot promise that I will find anything though. These experiments were performed between 2003 and 2006. My policy is to retain all original materials for at least 10 years. Older materials have occasionally been non-systematically retained. , 
 In Jan 2020 I have alerted the Editor-in-Chief of J Neuroimmunol of the issues raised above. I shall submit a report to the journal as soon as I will have achieved clarity on what exactly was done by whom, and why. This is not entirely straightforward since the relevant experiments were performed 16 years ago (they were published in 2007). Nevertheless, I maintain long-term experimental records of most of my lab s research (in many cases 30 years) which I hope will help me clarify these issues and correct the scientific record as appropriate. , 
 Any update on this case, Dr. Aguzzi? Were you able to find the original photos and send in a correction? ,
Trypsin-Like Serine Proteases in Lutzomyia longipalpis – Expression, Activity and Possible Modulation by Leishmania infantum chagasi
Authors: Claudia Masini d&#x27;Avila-Levy
Adriana Pereira Oliveira de Araújo
Erich Loza Telleria
Yara Maria Traub-Csekö
Nágila Francinete Secundino
Journal: PLoS ONE (2010)
Discipline: Multidisciplinary
Keywords: Midgut enzymatic activity; Trypsins; Lutzomyia longipalpis; Leishmania; Vector
Affiliations: Laboratório de Biologia Molecular de Parasitas e Vetores, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, Rio de Janeiro, Brazil.

Abstract:  Background: Midgut enzymatic activity is one of the obstacles that Leishmania must surpass to succeed in establishing infection. Trypsins are abundant digestive enzymes in most insects. We have previously described two trypsin cDNAs of L. longipalpis: one (Lltryp1) with a bloodmeal induced transcription pattern, the other (Lltryp2) with a constitutive transcription pattern. We have now characterized the expression and activity of trypsin-like proteases of Lutzomyia longipalpis, the main vector of visceral leishmaniasis in Brazil. Methodology and principal findings: In order to study trypsin expression profiles we produced antibodies against peptides specific for Lltryp1 and Lltryp2. The anti-Lltryp1-peptide antibody revealed a band of 28 kDa between 6 and 48 hours. The anti-Lltryp2 peptide antibody did not evidence any band. When proteinaceous substrates (gelatin, hemoglobin, casein or albumin) were co-polymerized in polyacrylamide gels, insect midguts obtained at 12 hours after feeding showed a unique proteolytic pattern for each substrate. All activity bands were strongly inhibited by TLCK, benzamidine and 4-amino-benzamidine, indicating that they are trypsin-like proteases. The trypsin-like activity was also measured in vitro at different time points after ingestion of blood or blood containing Leishmania infantum chagasi, using the chromogenic substrate BArhoNA. L. longipalpis females fed on blood infected with L. i. chagasi had lower levels of trypsin activity after 12 and 48 hours than non-infected insects, suggesting that the parasite may have a role in this modulation. Conclusions and significance: Trypsins are important and abundant digestive enzymes in L. longipalpis. Protein production and enzymatic activity followed previously identified gene expression of a blood modulated trypsin gene. A decrease of enzymatic activity upon the parasite infection, previously detected mostly in Old World vectors, was detected for the first time in the natural vector-parasite pair L. longipalpis-L. i. chagasi. 

Retracted: No

PubPeer comments:
 Fig. 6 - more similar than expected ![file] , 
 Figure 2: More similar than expected. Could authors check it please? ![file] ,
The ability of E1A to rescue ras-induced premature senescence and confer transformation relies on inactivation of both p300/CBP and Rb family proteins
Authors: Qingdong Deng
Rong Liao
Peiqing Sun
Gerhard Fuhrmann
Yilei Li
Donato Tedesco
Journal: Cancer Research (2005)
Discipline: CLINICAL MEDICINE
Keywords: oncogenic ras; premature senescence; senescence bypass; adenoviral oncoprotein E1A; Rb-binding
Affiliations: Department of Molecular Biology, The Scripps Research Institute, La Jolla, California 91037, USA.

Abstract:  In primary cells, oncogenic ras induces a stable growth arrest known as premature senescence. Ras-induced premature senescence is considered as a tumor-suppressing defense response that needs to be bypassed before oncogenic potential ras can be revealed. To gain insights into the mechanism of senescence bypass during oncogenic transformation, we dissected the activities of an adenoviral oncoprotein E1A, which is capable of overcoming ras-induced senescence. Our results have indicated that the senescence bypassing activity resides in the NH2 terminus and requires both Rb-binding and p300/CBP-binding functions of E1A. Although interference with the p16(INK4A)/Rb pathway or inactivation of p300/CBP alone did not lead to senescence bypass, these two types of genetic alterations complemented the Rb-binding defective and the p300/CBP-binding defective mutants of E1A, respectively, to rescue premature senescence. Therefore, genetic alterations disrupting the p16(INK4A)/Rb pathway or the p300/CBP functions both contribute to the bypass of senescence. We further showed that p300/CBP were essential for ras-induced p53 activity, providing a potential mechanism underlying the important role of p300/CBP in senescence. Furthermore, p300/CBP inactivation led to cellular transformation in cooperation with the p300/CBP-binding defective E1A mutants, MDM2 and Ha-RasV12. These results have shown that p300 and CBP are integral components of the pathway that mediates ras-induced senescence. The critical role of p300 and CBP in the senescence response that limits the oncogenic potential of ras has provided a mechanistic basis for the tumor-suppressing function of these proteins. 

Retracted: No

PubPeer comments:
 2020 retraction. https: www.nature.com articles s41380-020-0854-x.pdf The Editor-in-Chief and publisher have retracted this article [1] after an investigation by Arizona State University concluded that Figs. 1c and 4a had been manipulated and falsified by one or more of the authors. The Editor-in-Chief therefore no longer has confidence in the validity of the results and conclusions presented in this article. A. Caccamo, C. Branca and S Oddo agree with this retraction. E. Ferreira has not responded to correspondence related to this retraction. Reference 1. Caccamo A, Ferreira E, Branca C, Oddo S. p62 improves ADlike pathology by increasing autophagy. Mol Psychiatry. 2017;22:865u201373. ,