Targeting of GSK-3β by miR-214 to facilitate gastric cancer cell proliferation and decrease of cell apoptosis
Authors: H-L Li
J-H Cui
S Liang
G-Y Han
Journal: European review for medical and pharmacological sciences (2018)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Wnt/β-catenin pathway; GSK-3β; miR-214; gastric cancer; proliferation
Affiliations: The 2nd Department of General Surgery, Hongqi Hospital Affiliated to Mudanjiang Medical University, Mudanjiang, Heilongjiang, China. .

Abstract:  Objective: Wnt/β-catenin pathway regulates cell proliferation and apoptosis. GSK-3β degrades β-catenin and negatively regulates Wnt/β-catenin pathway. A previous study indicated that the GSK-3β expression was significantly reduced in gastric cancer, along with the increase of miR-214 expression. Bioinformatics analysis revealed complementary binding sites between miR-214 and 3'-UTR of GSK-3β mRNA. This study investigated the regulatory role and related mechanism of miR-214 in the proliferation and apoptosis of gastric cancer cells. Patients and methods: Gastric cancer tissues were collected from patients and the expressions of miR-214, GSK-3β and β-catenin were determined. Dual luciferase reporter gene assay was used to study the regulatory role between miR-214 and GSK-3β. Expressions of miR-214, GSK-3β, β-catenin and survivin from GES-1 and MKN-28 cells were detected. Flow cytometry was used to measure cell proliferation and apoptosis. In vitro cultured MKN-28 cells were treated with miR-214 inhibitor and/or pSicoR-GSK-3β. Levels of GSK-3β, β-catenin and survivin were detected, cell apoptosis was evaluated by flow cytometry and proliferation was tested by EdU staining. Results: Compared to normal gastric mucosa, the levels of miR-214 and β-catenin were elevated, and the expression of GSK-3β was decreased in gastric cancer tissues. Compared to GES-1 cells, the expressions of miR-214, β-catenin and survivin in MKN-28 cells were upregulated, along with downregulation of GSK-3β expression. The proliferation was enhanced whilst apoptosis was suppressed. After the transfection of miR-214 inhibitor and/or pSicoR-GSK-3β, GSK-3β expression was induced in MKN-28 cells while β-catenin and survivin expressions were inhibited, along with the increase of cell apoptosis. Conclusions: MiR-214 decreases GSK-3β expression and promotes the pathogenesis of gastric cancer. The inhibition of miR-214 reduces the proliferation of gastric cancer cells via upregulation of GSK-3β and suppression of Wnt/β-catenin signal pathway, which provides fundamental support for the future therapy of gastric cancer. 

Retracted: Yes

PubPeer comments:
 This paper was one of many listed as the work of a papermill, on account of its stylistic features. https: docs.google.com spreadsheets d 1qBqQMXgzxoBd5bTbqdMuapGheupE5bdIopypju417NM edit#gid=0 Some time in the last week or so, the journal wished it into the cornfield: https: www.europeanreview.org article 22245 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, u201cTargeting of GSK-3u03b2 by miR-214 to facilitate gastric cancer cell proliferation and decrease of cell apoptosis, by H.-L. Li, S. Liang, J.-H. Cui, G.-Y. Han, published in Eur Rev Med Pharmacol Sci 2018; 22 (1): 127-134u2013DOI: 10.26355 eurrev_201801_14109u2013PMID: 29364479u201d has been withdrawn. The Publisher apologizes for any inconvenience this may cause. ,