Downregulating circRNA_0044516 Inhibits Cell Proliferation in Gastric Cancer Through miR-149/Wnt1/beta-catenin Pathway

pubmed: wnt1 2021-02-26

J Gastrointest Surg. 2020 Nov 2. doi: 10.1007/s11605-020-04834-w. Online ahead of print.

ABSTRACT

BACKGROUND: Circular RNAs (circRNAs) play important roles in the progression of gastric cancer (GC). The Wnt1/β-catenin pathway can promote the proliferation of GC cells. This study aimed to explore whether circRNA_0044516 can regulate the proliferation of GC cells by modulating the Wnt1/β-catenin pathway.

METHODS: The expression of circRNA_0044516, miR-149, Wnt1, and β-catenin in GC tissues or cells was detected by qRT-PCR and western blot. Cell viability and apoptosis were measured by CCK-8 and flow cytometry assays, respectively. The interaction between circRNA_0044516 and miR-149 was determined by luciferase reporter and RNA pull-down assays.

RESULTS: Upregulated circRNA_0044516 was found in GC tissues and cell lines. Downregulating circRNA_0044516 inhibited the viability and promoted apoptosis of GC cells. CircRNA_0044516 targeted miR-149, and its downregulation elevated miR-149 level in GC cells. Mechanistically, silencing circRNA_0044516 reduced the protein level of Wnt1 and β-catenin through miR-149, and finally suppressed viability and contributed to apoptosis of GC cells. Moreover, circRNA_0044516 knockdown inhibited the tumor growth of HGC-27 cells in nude mice.

CONCLUSIONS: Our results indicated an important role of circRNA_0044516 in GC and elucidated that downregulation of circRNA_0044516 inhibits the proliferation of GC cells through miR-149/Wnt1/β-catenin.

PMID:33140323 | DOI:10.1007/s11605-020-04834-w