Circ_0000467 regulates proliferation, migration, invasion, and apoptosis in gastric cancer by targeting the miR-622/ROCK2 axis

• Shengquan Tan ^[1] ; Lingbo Hu ^[1] ; Rui Lei ^[1] ; Ruo Wang ^[1] ; Jiaquan Chen ^[1]
  1. [1] The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi City, Hubei Province, China
• Localización: Histology and histopathology: cellular and molecular biology, ISSN-e 1699-5848, ISSN 0213-3911, Vol. 38, Nº. 2, 2023, págs. 185-197
• Idioma: inglés
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• Resumen

  • y. 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 coiledcoil-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-offunction 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 miR622, 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.