Effects of microRNA-136 on melanoma cell proliferation, apoptosis, and epithelial–mesenchymal transition by targetting PMEL through the Wnt signaling pathway
Authors: Zhi-Jun Liu
Jiu-Jiang Wang
Zhao Han
Zhi-Feng Li
Ling Zhang
Xiao-Jing Li
Journal: Bioscience Reports (2017)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Cell proliferation; Epithelial-mesenchymal transition; Melanoma cells; PMEL; Wnt signaling pathway
Affiliations: Department of Dermatology, Affiliated Hospital of Hebei University of Engineering, Handan 056002, P.R. China., Department of Dermatology, Affiliated Hospital of Hebei University of Engineering, Handan 056002, P.R. China  .

Abstract:  The study aims to evaluate the effects of miR-136 on the proliferation, apoptosis, and epithelial-mesenchymal transition (EMT) of melanoma cells by targetting premelanosome protein (PMEL) through the Wnt signaling pathway. After establishment of melanoma mouse models, melanoma (model group) and normal tissues (normal group) were collected. Immunohistochemistry was performed to determine PMEL protein concentration. Mouse melanoma cells were assigned into control, blank, negative control (NC), miR-136 mimics, miR-136 inhibitors, siRNA-PMEL, and miR-136 inhibitors + siRNA-PMEL, LiC1 (Wnt signaling pathway activator), and siRNA-PMEL+ LiCl groups. MTT, Scratch test, Transwell assay, and flow cytometry were performed to measure cell proliferation, migration, invasion, and apoptosis. Quantitative real-time PCR (qRT-PCR) and Western blotting were performed to evaluate miR-136, PMEL, β-catenin, Wnt3a, Bcl-2, Bax, Caspase, E-cadherin, and N-cadherin expressions. PMEL is highly expressed in melanoma tissues. MiR-136, Bax, Caspase, and E-cadherin expressions decreased in the model group, whereas PMEL, β-catenin, Bcl-2, Wnt3a, and N-cadherin expressions increased. Bax, Caspase, and E-cadherin expressions increased in the miR-136 mimics and siRNA-PMEL groups, whereas the expressions decreased in the miR-136 inhibitors group and LiC1 group. PMEL, β-catenin, Bcl-2, Wnt3a, and N-cadherin expressions, cell proliferation, migration, and invasion decreased, and the apoptosis rate inceased in the miR-136 mimics and siRNA-PMEL groups; whereas the tendencies were opposite to those in the miR-136 inhibitors group and LiC1 group. In the siRNA-PMEL+ LiCl group, PMEL expression decreased. These findings indicated that overexpression of miR-136 inhibits melanoma cell EMT, proliferation, migration, invasion, and promotes apoptosis by targetting PMEL through down-regulation of the Wnt signaling pathway. 

Retracted: No

PubPeer comments:
  The results of Hematoxylin and Eosin staining (400u00d7) Normal and Model differ mainly in scale. ![file] , 
 Fig 6B.  The protein expressions of Bax, Caspase, E-cadherin, PMEL, u03b2-catenin, Bcl-2, Wnt3a, and N-cadherin in each group after transfection ... (B) gray value analyzed by Western blotting ![file] 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)] . , 
 Fig 9A.  Effects of miR-136 on cell invasion of B16 cells in each group (A) Cell invasion of each group under a microscope; ![file] Comparing with Fig 8A,C from [Li et al (2017)] : ![file] ![file] Two panels appear to match. They are not identical, each having acquired additional cells. , 
 My bad, comment in wrong thread. , 
 Expression of Concern, [28 August 2020] .  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 [23 April 2021](10.1042 BSR-20170743_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 duplication in Figure 1 as well as duplication in the Western blots of Figure 6B, of which parts appear in multiple published articles from different author groups. The authors have been contacted in regard to the retraction, and disagree with the Journal s decision to retract the article. The authors state that the duplications are due to errors being made by the authors during the submission of the article. Given the extent of the issues raised, the Editorial Board stands by the decision to retract the article. ,