MicroRNA-575 regulates development of gastric cancer by targeting PTEN

• Main Authors: Ya-nan Wang, Fang Xu, Pei Zhang, Pan Wang, Ya-ning Wei, Chen Wu, Shu-jie Cheng
• Format: Article
• Language: English
• Published: Elsevier 2019-05-01
• Series: Biomedicine & Pharmacotherapy
• Subjects: Gastric cancer; microRNA-575; PTEN; Proliferation; Apoptosis
• Online Access: http://www.sciencedirect.com/science/article/pii/S0753332219300022

MicroRNA-575 (miR-575) is oncogene in many tumors. However, the role of miR-575 in the progression of gastric cancer (GC) is still unknown. The aim of this study was to identify whether miR-575 play a role in the development of GC. We obtained GC cell lines, GC tissues from 40 patients to measure the levels of miR-575 and its predicted target PTEN by using RT‑PCR, immunohistochemistry or western blot analysis. MGC-803 cells were transfected with miR-575 inhibitor, and cells viability and apoptosis were measured. miR-575 aberrantly up-regulated in GC tissues and GC cell lines compared with corresponding control. In cell lines, MGC‑803 expressed highest level of miR-575 among the tested cells. The level of miR-575 was correlated with the tumor size, AJCC stage and prognosis, but not with the other clinical parameters. Knockdown of miR-575 inhibited proliferation and promoted apoptotic death of MGC-803 cells both in vitro and vivo. PTEN levels (both mRNA and protein) were remarkably decreased in cancer tissues compared with the paired-adjacent tissues, and negatively correlated with miR-575 in the tissues. By using luciferase reporter assay, we found PTEN was a direct downstream target of miR-575, and negatively regulated by miR-575 via targeting its 3′UTR. Knockdown or overexpression of miR-575 in MGC-803 cells negatively regulated PTEN expression. Finally, silencing PTEN partially impaired anti-proliferative effects of miR-575 inhibitor. miRNA-575 serves a pivotal role in GC as a cancer promoter gene by targeting PTEN to regulate proliferation and apoptosis of the cancer cells.