Downregulation of circ-SFMBT2 blocks the development of gastric cancer by targeting the miR-885-3p/CHD7 pathway.

Yuqi He, Zhongliang Zhang, Zinian Wang, Yigang Jiao, Qi Kang, Jingzhe Li

Anti-cancer drugs 2022 Jan 01

filter terms:

Accumulating evidence insists that circular RNAs (circRNAs) play important roles in the development of human cancers, including gastric cancer. This study aimed to investigate the role of circ-SFMBT2 and provide a potential mechanism to explain its function. The expression of circ-SFMBT2, miR-885-3p and chromodomain-helicase-DNA-binding protein 7 (CHD7) mRNA was determined by quantitative real-time PCR (qRT-PCR), and the protein level of CHD7 was determined by western blot. To investigate the function of circ-SFMBT2 in vitro, the effects of circ-SFMBT2 on cell viability, colony formation, apoptosis, migration and invasion were assessed using cell counting kit-8 assay, colony formation assay, flow cytometry assay, wounding healing assay and transwell assay, respectively. The indicators of oxidative stress were assessed using matched kits. Besides, the function of circ-SFMBT2 was also investigated in animal models. The relationship between miR-885-3p and circ-SFMBT2 or CHD7 was verified by dual-luciferase reporter assay and RNA immunoprecipitation assay. Circ-SFMBT2 and CHD7 were upregulated, whereas miR-885-3p was downregulated in gastric cancer tissues and cells. In functional assay, circ-SFMBT2 knockdown suppressed gastric cancer cell viability, colony formation ability, migration, invasion and oxidative stress but induced apoptosis, and circ-SFMBT2 downregulation also blocked tumor growth in vivo. In mechanism analysis, circ-SFMBT2 regulated CHD7 expression by sponging its target miRNA, miR-885-3p. Rescue experiments manifested that miR-885-3p inhibition reversed the effects of circ-SFMBT2 knockdown, and CHD7 overexpression abolished the antitumor role of miR-885-3p overexpression. Moreover, circ-SFMBT2 knockdown inactivated the Wnt/β-catenin signaling pathway. Circ-SFMBT2 downregulation repressed the development of gastric cancer partially by controlling the miR-885-3p/CHD7 axis, which might be a novel strategy to inhibit gastric cancer progression. Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.

Citation

Yuqi He, Zhongliang Zhang, Zinian Wang, Yigang Jiao, Qi Kang, Jingzhe Li. Downregulation of circ-SFMBT2 blocks the development of gastric cancer by targeting the miR-885-3p/CHD7 pathway. Anti-cancer drugs. 2022 Jan 01;33(1):e247-e259