MiR-155 affects renal carcinoma cell proliferation, invasion and apoptosis through regulating GSK-3Œ≤/Œ≤-catenin signaling pathway
Authors: C-H Zhang
W-Z Yang
R-J Wei
Journal: European Review for Medical and Pharmacological Sciences (2017)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Glycogen Synthase Kinase-3Œ≤; GSK-3Œ≤; Wnt/Œ≤-catenin signaling pathway; MicroRNA-155; MiR-155
Affiliations: Department of Urology Surgery, The First Central Hospital of Baoding, Baoding, Hebei, China. .

Abstract:  Objective: Glycogen Synthase Kinase-3Œ≤ (GSK-3Œ≤) negatively regulates Wnt/Œ≤-catenin signaling pathway through degrading Œ≤-catenin protein. It plays an inhibitory role in various tumors, while the influence in the pathogenesis of renal carcinoma has not been elucidated. MicroRNA-155 (MiR-155) was found to be upregulated in renal carcinoma tissue. Bioinformatics analysis revealed the complementary binding site between miR-155 and 3'-UTR of GSK-3Œ≤. This study investigated the influence of miR-155 in regulating GSK-3Œ≤ expression, Wnt/Œ≤-catenin signaling pathway activity, and renal carcinoma cell proliferation, invasion, and apoptosis. Patients and methods: The targeted regulatory relationship between miR-155 and GSK-3Œ≤ were tested by dual luciferase assay. Renal carcinoma tissue and benign renal tissue were collected to detect miR-155 and GSK-3Œ≤ expressions. MiR-155, GSK-3Œ≤, and Œ≤-catenin levels were compared between HK-2 and 786-O cells. Renal carcinoma 786-O cells were cultured in vitro and divided into four groups, including miR-NC, anti-miR-155, pIRES2-blank, and pIRES2-GSK-3Œ≤ groups. Cell apoptosis was evaluated by flow cytometry. Cell invasion was determined by transwell assay. Cell proliferation was assessed by EdU staining. Results: MiR-155 targeted regulated GSK-3Œ≤ expression. MiR-155 and Œ≤-catenin expressions were significantly increased, while GSK-3Œ≤ level was significantly declined in renal carcinoma tissue compared with benign renal tissue. MiR-155 and Œ≤-catenin expressions were significantly elevated, whereas GSK-3Œ≤ level was significantly downregulated in 786-O cells compared with HK-2 cells. Anti-miR-155 or pIRES2-GSK-3Œ≤ transfection significantly up-regulated GSK-3Œ≤ expression, attenuated Œ≤-catenin level, restrained cell proliferation and invasion, and enhanced cell apoptosis. Conclusions: MiR-155 promoted renal carcinoma pathogenesis. Inhibition of miR-155 increased GSK-3Œ≤ expression, attenuated Wnt/Œ≤-catenin signaling pathway, weakened proliferation and invasion, and facilitated apoptosis in renal carcinoma cells. 

Retracted: Yes

PubPeer comments:
 In this study, the authors uses the method of meta-analysis to explore the association of interleukin-10 promoter polymorphisms and susceptibility to diffuse large B-cell lymphoma. However, there are several major deficiencies in this study. 1. In Kube et al study, they just showed that interleukin-10 gene promoter polymorphism u22121087AG does not correlate with clinical outcome in non-Hodgkin s lymphoma. It should be noted that what authors concerned about is clinical outcome, not susceptibility. 2. The article  Berglund et al., 2005 M. Berglund, U. Thunberg, G. Roos, R. Rosenquist, G. Enblad The interleukin-10 gene promoter polymorphism (u20131082) does not correlate with clinical outcome in diffuse large B-cell lymphoma Blood, 105 (2005), pp. 4894-4895 is letter to the editor, is the data from this letter to the editor suitable for inclusion in the analysis? 3. Similarly,in Lech-Maranda et al study, they just showed that Interleukin-10 gene promoter polymorphisms influence the clinical outcome of diffuse large B-cell lymphoma. It should be noted that what authors concerned about is clinical outcome, not susceptibility. ,