Circ_0011058 facilitates proliferation, angiogenesis and radioresistance in papillary thyroid cancer cells by positively regulating YAP1 via acting as miR-335-5p sponge

Circ_0011058 通过充当 miR-335-5p 海绵正向调节 YAP1 促进乳头状甲状腺癌细胞的增殖、血管生成和放射抗性

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作者:Zhenhua Zhang, Wei Wang, Zijie Su, Ji Zhang, Huixia Cao

Background

Circular RNAs (circRNAs) are reported to be associated with multiple biological processes in human cancers. However, there are still numerous circRNAs whose functions remain unclear. The

Conclusion

Circ_0011058 promoted PTC cell proliferation, angiogenesis and radioresistance by upregulating YAP1 via acting as miR-335-5p sponge.

Methods

Quantitative real-time PCR (qPCR) was utilized to detect the expression of circ_0011058, microRNA-335-5p (miR-335-5p) and Yes-associated Protein 1 (YAP1). Cell proliferation was detected using cell counting kit-8 (CCK-8) assay and EdU assay. Cell apoptosis was detected by flow cytometry assay. Angiogenesis ability was assessed using tube formation assay. The expression of angiogenesis-related proteins and YAP1 protein was detected by western blot. Radioresistance was examined using colony formation assay. The binding relationship between miR-335-5p and circ_0011058 or YAP1 was verified by dual-luciferase reporter assay, pull-down assay and RIP assay. Xenograft models were constructed to ensure the role of circ_0011058.

Results

Circ_0011058 expression was aberrantly elevated in PTC tissues and cells. The downregulation of circ_0011058 suppressed proliferation, angiogenesis and radioresistance in PTC cells. MiR-335-5p was defined as a target of circ_0011058, and miR-335-5p inhibition reversed the effects of circ_0011058 downregulation. In addition, YAP1 was a target of miR-335-5p, and circ_0011058 positively regulated YAP1 expression by targeting miR-335-5p. MiR-335-5p restoration inhibited proliferation, angiogenesis and radioresistance in PTC cells, while YAP1 overexpression abolished these effects. Animal study showed that circ_0011058 knockdown inhibited tumor growth in vivo.

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