Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

MiR-331-5p suppresses gastric cancer cell proliferation, migration, invasion, and glycolysis via targeting PFKFB3

Guijun Wei , Lei Qiu, Huifei Lu Zhongmin Deng

Department of Gastroenterology, No. 1 People's Hospital of Huzhou, Huzhou City, Zhejiang Province 313000, China;

For correspondence:- Guijun Wei Email: guijun_wei@163.com

Accepted: 28 October 2020 Published: 30 November 2020

Citation: Wei G, Qiu L, Lu H.Deng Z. MiR-331-5p suppresses gastric cancer cell proliferation, migration, invasion, and glycolysis via targeting PFKFB3. Trop J Pharm Res 2020; 19(11):2265-2272 doi: 10.4314/tjpr.v19i11.3

© 2020 The authors.
This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) and the Budapest Open Access Initiative (http://www.budapestopenaccessinitiative.org/read), which permit unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited..

Abstract

Purpose: To examine the role of microRNAs (miRNAs), miR-331-5p, in gastric cancer (GC).

Methods: The mRNA level of miR-331-5p and protein level of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3 (PFKFB3) were determined using quantitative real-time reverse transcription–polymerase chain reaction (qRT–PCR) and western blotting, respectively. The cell viability and proliferation of the two GC cell lines (AGS and MKN45) were evaluated using Cell Counting Kit-8 (CCK-8) and bromodeoxyuridine (BrdU) assays. Cell migration and invasion of AGS and MKN45 were evaluated using wound healing and invasion assays, respectively. Potential interactions between miR-331-5p and PFKFB3 were assessed by luciferase activity assay, while the effects of the interactions on cell physiology and metabolism were investigated in cells overexpressing both miR-331-5p and PFKFB3.

Results: MiR-331-5p overexpression inhibited cell proliferation, suppressed migration and invasion, and inhibited glycolysis in AGS and MKN45 cells. The mRNA for the glycolytic regulatory enzyme PFKFB3 was shown to be a direct target of miR-331-5p and modulated by miR-331-5p. In rescue experiments, PFKFB3 reversed the miR-331-5p-induced inhibition of proliferation, migration, invasion, and glycolysis in AGS cells.

Conclusion: This work supports a role for miR-331-5p through the modulation of PFKFB3 activity in GC in vivo, thus providing insight into novel potential therapies for the treatment of GC.

Keywords: Gastric cancer, MiR-331-5p, Cell proliferation, Glycolysis, PFKFB3