Publication: Circular RNA circ_SKA3 enhances gastric cancer development by targeting miR-520h
Authors
Wang, Chuntao ; Jiang, Hao ; Peng, Jiaqun ; Weng, Duanshun ; Zhang, Yu ; Zhou, Yanxun ; Zhang, Qin
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Publisher
Universidad de Murcia, Departamento de Biologia Celular e Histiologia
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DOI
https://doi.org/ 10.14670/HH-18-521
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info:eu-repo/semantics/article
Description
Abstract
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.
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Citation
Histology and Histopathology Vol. 38, nº3 (2023)
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