MicroRNA-31 triggers G2/M cell cycle arrest, enhances the chemosensitivity and inhibits migration and invasion of human gastric cancer cells by downregulating the expression of zeste homolog 2 (ZH2)
Authors: Peng Hua
Hao-Dong Wang
Ke-Kang Sun
Xiao-Jun Shen
Yi-Fan Zhang
Gang Liu
Ming-Qiang Gan
Dong Yang
Xiao-Yang Wu
Journal: Archives of Biochemistry and Biophysics (2019)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Cell cycle arrest; Chemosensitivity; Gastric cancer; Proliferation; microRNA.
Affiliations: Clinical Medical College of Jiangsu University, Department of Gastrointestinal Surgery, Kunshan First People's Hospital Affiliated to Jiangsu University, Kunshan, Jiangsu, 215300, China., Clinical Medical College of Jiangsu University, Department of Gastrointestinal Surgery, Kunshan First People's Hospital Affiliated to Jiangsu University, Kunshan, Jiangsu, 215300, China. Electronic address: .

Abstract:  Gastric cancer is the second most leading cause of cancer related mortality across the world over. Although the incidence of GC has declined to some extent but it is still the fourth highly diagnosed cancer across the world. GC generally remains undiagnosed till advanced stages due to unavailability of biomarkers and when diagnosed it becomes difficult to manage due to the lack of therapeutic targets and efficient chemotherapy. There are concrete evidences suggesting that miRNAs may prove important therapeutic targets for the treatment of devastating diseases such as cancer. The study was designed to investigate the tumor suppressive role of miR-31 via regulation of zeste homolog 2 (ZH2). It was found that miR-31 is significantly downregulated in GC cell lines. Overexpression of miR-31 causes significant (P &lt; 0.05) decrease in the viability and colony formation via initiation of G2/M cell cycle arrest of the AGS cancer cells. Moreover, miR-31 overexpression also enhanced the chemosensitivity of miR-31 to the anticancer drug 5-fluorouracil. In silico analysis together with dual luciferase reporter assay indicated zeste homolog 2 (ZH2) to be the potential target of miR-31 in AGS cells. Investigation of ZH2 expression in GC cell lines showed it to be significantly (P &lt; 0.05) upregulated. Nonetheless, overexpression of miR-31 in AGS cells resulted in the suppression of ZH2 expression. Additionally, silencing of ZH2 in the AGS cells also caused inhibition of AGS cell proliferation and colony formation via G2/M arrest. Moreover, overexpression of ZH2 could at least partially reverse the tumor suppressive effects of miR-31 indicating direct involvement of ZH2 in the miR-31 mediated inhibitory effects on AGS cell proliferation. Finally, miR-31 overexpression caused significant (P &lt; 0.05) inhibition of the migration and invasion of the AGS gastric cancer cells. The overexpression of miR-31 also caused downregulation of mesenchymal markers (Vimentin and N-cadherin) and upregulation of epithelial marker (E-cadherin) protein expression was in AGS cells. It is therefore concluded that miR-31 acts as a tumor suppressor and may prove essential in the treatment of GC. 

Retracted: No

PubPeer comments:
 Fig 4D.  Fig. 4. Silencing of ZH2 inhibits the proliferation of gastric cancer cells ... (D) Colony formation of NC and Si-ZH2 transfected AGS cells  For comparison with *[above]* Fig 1D from [Yin et al (2019)] .  Colony formation of the NC and Si-PPMD1 transfected HT-29 cells . *[below]* Fig 4C from [Si et al (2019)] .  Colony formation of NC and pcDNA-CUL5 transfected SK-OV3 and OVACAR-3 cells .  ,