Effects of microRNA-374 on proliferation, migration, invasion, and apoptosis of human SCC cells by targeting Gadd45a through P53 signaling pathway
Authors: Bao-Guo Liu
Zhao Liu
Jiu-Jiang Wang
Zhao Han
Zhi-Feng Li
Xiao-Jing Li
Journal: Bioscience Reports (2017)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Apoptosis; Gadd45a; MicroRNA-374; P53 signaling pathway; Proliferation
Affiliations: Department of Dermatology, Affiliated Hospital of Hebei Engineering University, Handan 056002, P.R. China., Department of Dermatology, Affiliated Hospital of Hebei Engineering University, Handan 056002, P.R. China  .

Abstract:  The present study investigated the effects of microRNA-374 (miR-374) on human squamous cell carcinoma (SCC) cell proliferation, migration, invasion, and apoptosis through P53 signaling pathway by targeting growth arrest and DNA-damage-inducible protein 45 Œ± (Gadd45a). Skin samples were collected from patients with skin SCC and normal skin samples. Expression of miR-374, Gadd45a, P53, P73, P16, c-myc, bcl-2, Bax, caspase-3, and caspase-9 were detected using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. A431 and SCL-1 cells were divided into blank, negative control (NC), miR-374 mimics, miR374 inhibitors, siRNA-Gadd45a, and miR-374 inhibitors + siRNA-Gadd45a groups. Their proliferation, migration, invasion, cell cycle, and apoptosis were evaluated by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay, scratch test, Transwell assay, and flow cytometry. SCC skin tissues exhibited decreased expression of miR-374, P73, P16, Bax caspase-3 and caspase-9, and increased levels of Gadd45a, P53, c-myc, and Bcl-2 compared with the normal skin tissues. The miR-374 inhibitors group exhibited decreased expression of miR-374, P73, P16, Bax caspase-3 and caspase-9, and increased expression of Gadd45a, P53, c-myc, and Bcl-2, enhanced cell proliferation, migration, and invasion, and reduced apoptosis compared with the blank and NC groups; the miR-374 mimics group followed opposite trends. Compared with the blank and NC groups, the miR-374 inhibitors + siRNA-Gadd45a group showed decreased miR-374 level; the siRNA-Gadd45a group showed elevated levels of P73, P16, Bax, caspase-3 and caspase-9, decreased levels of Gadd45a, P53, c-myc, and Bcl-2, reduced cell proliferation, migration, and invasion, and accelerated apoptosis. miR-374 induces apoptosis and inhibits proliferation, migration, and invasion of SCC cells through P53 signaling pathway by down-regulating Gadd45a. 

Retracted: No

PubPeer comments:
 Figure 8C has what appears to be an image duplication  , 
 Fig 5 C,D.  The levels of miR-374, Gadd45a, P53, P73, P16, c-myc, Bcl-2, Bax, caspase-3, and caspase-9 in normal cells, and A431 and SCL-1 cells in blank, NC, miR-374 mimics, miR374 inhibitors, siRNAu2013Gadd45a, and miR-374 inhibitors + siRNAu2013Gadd45a groups ... (C) The gray values of Gadd45a, P53, P73, P16, c-myc, Bcl-2, Bax, caspase-3, and caspase-9 protein bands for A431 cells, evaluated using Western blot assay. (D) The gray values of Gadd45a, P53, P73, P16, c-myc, Bcl-2, Bax, caspase-3, and caspase-9 protein bands for SCL-1 cells, evaluated using Western blot assay. Loading controls are surprisingly similar after a horizontal flip and vertical expansion.  All the protein blobs seem to come from the limited gamut shown in this montage:  Clockwise from upper left, Fig 6B,  protein band graph , from  MicroRNA-374 Exerts Protective Effects by Inhibiting SP1 Through Activating the PI3K Akt Pathway in Rat Models of Myocardial Ischemia-Reperfusion After Sevoflurane Preconditioning [(Zhang et al 2018)] . Fig 4D,  GLP-1R and CREB proteins in the myocardium of mice in each group examined by western blotting , from  Suppression of Long Non-Coding RNA LINC00652 Restores Sevoflurane-Induced Cardioprotection Against Myocardial Ischemia-Reperfusion Injury by Targeting GLP-1R Through the cAMP PKA Pathway in Mice [(Zhang et al 2018)] . Fig. 6B,  ELISA and western blot analysis were applied to determine the miR- 495 expression and mRNA and protein expression of NLRP3, TNF-u03b1, IL-1u03b2, IL-18 and caspase-1 , from  MicroRNA-495 Ameliorates Cardiac Microvascular Endothelial Cell Injury and Inflammatory Reaction by Suppressing the NLRP3 Inflammasome Signaling Pathway [(Zhou et al 2018)] . Fig 6B,  WB images showing protein expression of different genes in each group , from  MicroRNA-27a Suppresses Detrusor Fibrosis in Streptozotocin-Induced Diabetic Rats by Targeting PRKAA2 Through the TGF-u03b21 Smad3 Signaling Pathway . [(Wu et al 2018)] . Fig 11E,  protein bands of each factor in ASMCs of asthma mice in each group detected by western blot analysis , from  MicroRNA-485 Modulates the TGF-u03b2 Smads Signaling Pathway in Chronic Asthmatic Mice by Targeting Smurf2 . [(Wang et al 2018)] . , 
 #1 Additional concerns.  , 
 #1 8A C again:   More overlaps with Fig 9 of [Wang et al (2017)] .  Marked panels are not identical, each having acquired additional cells. , 
 Figure 10A.  Cells apoptosis of normal cells, and A431 and SCL-1 cells in the blank, NC, miR-374 mimics, miR374 inhibitors, siRNAu2013Gadd45a, and miR-374 inhibitors + siRNAu2013Gadd45a groups, evaluated by flow cytometry (A) A431 cell apoptosis .  Panels are very similar to those in Fig 7C of [Pan et al (2018)] .  Changes in cell apoptosis and cell cycle distribution in the six groups. ... C, cell apoptosis analysis via flow cytometry .  , 
 Fig 8A.  Cell invasion of normal cells, and A431 and SCL-1 cells in the blank, NC, miR-374 mimics, miR374 inhibitors, siRNAu2013Gadd45a, and miR-374 inhibitors + siRNAu2013Gadd45a groups, evaluated by the Transwell assay (A) A431 cell invasion images :  Fig 6 of [Liu et al (2017)] .  The migration and invasion ability of the SK-NEP-1 cells after transfection in each group as detected by the Transwell assay .  Different cell types, different treatments, different authors, same panel. , 
 #1 Fig 8C again:  Fig 9A of [Lin et al (2017)] ,  Comparisons on cell invasion capacity in human PC SW1990 cells among different groups after transfection through transwell assy. Note: A, cell invasion conditions in different groups .  Different cells, different treatments, different authors, same panel. , 
 https: doi.org 10.1042 BSR-20170710_EOC The Editorial Office has been made aware of potential issues surrounding the scientific validity of this paper, hence has issued an expression of concern to notify readers whilst the Editorial Office investigates. , 
 Retracted [22 April 2021](10.1042 BSR-20170710_RET). -------------------------------------- This Retraction follows an Expression of Concern relating to this article previously published by Portland Press. This article is being retracted from Bioscience Reports at the request of the Editor-in-Chief and the Editorial Board following receipt of a notification from a reader, alerting the Editorial Board to images that have been duplicated (from within the same article and from other published articles) in Figures 5C, 5D, 8A, 8C and 10A. The authors were contacted regarding the concerns raised and wished to correct the article, however given the extent of the issues raised, the Editorial Board stands by the decision to retract the article. The authors disagree with the Journal s decision to retract the article and state that the duplications are due to errors being made by the authors during the submission of the article. ,