Background: Gastric cancer (GC) ranks fourth as a cause of cancer-induced mortality worldwide. Recently, some studies have demonstrated that circular RNAs (circRNAs) play vital roles in human cancers, including GC.
Methods: The expression levels of circ_0000467, microRNA-622 (miR-622), and Rho-associated coiled-coil-containing protein kinase2 (ROCK2) were determined by RT-qPCR assay. The protein expression was quantified by western blot assay. The interaction relationship between miR-622 and circ_0000467 or ROCK2 was confirmed by dual-luciferase reporter assay and RIP assay. The biological behaviors of GC cells including proliferation, apoptosis, migration, and invasion were determined by EdU assay, colony-forming assay, flow cytometry, and transwell assay. The effects of circ_0000467 silencing in vivo were assessed by a xenograft experiment in nude mice.
Results: MiR-622 was downregulated and ROCK2 was upregulated in GC tissues and cells. Loss-of-function experiment revealed that overexpression of miR-622 decreased proliferation, migration, and invasion while it increased apoptosis in GC cells. Furthermore, ROCK2 was a functional target of miR-622, and upregulation of ROCK2 abolished miR-622-induced effects on GC cells. What's more, circ_0000467 was upregulated in GC, and inhibition of miR-622 reversed silencing of circ_0000467-caused effects on GC cells, suggesting that miR-622 was a target of circ_0000467. The suppression of circ_0000467 was able to slow the tumor growth in vivo.
Conclusion: Mechanistically, circ_0000467 functioned as an oncogenic regulator in GC by specifically binding to miR-622 to upregulate ROCK2, which might be novel diagnostic markers for GC.
©The Author(s) 2023. Open Access. This article is licensed under a Creative Commons CC-BY International License.