Circular RNA circ_SKA3 enhances gastric cancer development by targeting miR-520h

• Chuntao Wang ^[1] ; Hao Jiang ^[1] ; Jiaqun Peng ^[1] ; Duanshun Weng ^[1] ; Yu Zhang ^[1] ; Yanxun Zhou ^[1] ; Qin Zhang
  1. [1] Suizhou Central Hospital, Suizhou, Hubei, China
• Localización: Histology and histopathology: cellular and molecular biology, ISSN-e 1699-5848, ISSN 0213-3911, Vol. 38, Nº. 3, 2023, págs. 317-328
• Idioma: inglés
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• Resumen

  • Purpose. To explore the mechanisms of action of circ_SKA3 in gastric cancer (GC), which are still not fully understood.

    Methods. Subcellular localization assay was used to analyze the localization of circ_SKA3, and Actinomycin D assay was applied to confirm the stability of circ_SKA3. The levels of circ_SKA3, microRNA (miR)- 520h, and cell division cycle 42 (CDC42) mRNA were gauged by quantitative real-time polymerase chain reaction (qRT-PCR). The protein levels of CDC42 and proliferating cell nuclear antigen (PCNA) were assessed by western blot. Cell proliferation, colony formation, cell cycle distribution, apoptosis, migration, and invasion were detected by 3-[4,5-dimethylthiazol-2-yl]- 2, 5-diphenyltetrazolium bromide (MTT), 5-Ethynyl-2’- Deoxyuridine (EdU) incorporation, colony formation, flow cytometry, and transwell assays, respectively.

    Directed relationship between miR-520h and circ_SKA3 or CDC42 was verified by a dual-luciferase reporter assay. Mouse xenograft experiments were used to elucidate the impact of circ_SKA3 in vivo.

    Results. Overexpression of circ_SKA3 was validated in GC tissues and cells. The down-regulation of circ_SKA3 suppressed proliferation, cell cycle progression, colony formation, migration, invasion, and promoted cell apoptosis in vitro, as well as weakening tumor growth in vivo. Circ_SKA3 directly bound to miR-520h, and circ_SKA3 regulated CDC42 expression through miR-520h. Circ_SKA3 exerted regulatory effects on GC cell behaviors by inhibiting miR-520h.

    Furthermore, CDC42 was a functional target of miR520h in regulating GC cell behaviors.

    Conclusion. Our findings established a strong molecular mechanism, the miR-520h/CDC42 axis, at least in part, for the oncogenic role of circ_SKA3 in GC.