circ_0002346 Suppresses Non-Small-Cell Lung Cancer Progression Depending on the Regulation of the miR-582-3p/STXBP6 Axis

circ_0002346 通过 miR-582-3p/STXBP6 轴的调节来抑制非小细胞肺癌进展

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作者:Weijie Wang, Yi Lin, Guanghui Zhang, Guofu Shi, Yongsheng Jiang, Wentao Hu, Wei Zuo

Background

Accumulating articles have reported the pivotal regulatory roles of circular RNAs (circRNAs) in non-small-cell lung cancer (NSCLC) tumorigenesis. Here, our

Conclusion

circ_0002346 overexpression suppressed the malignant properties of NSCLC cells by binding to miR-582-3p to induce the expression of STXBP6.

Methods

Cell proliferation ability was assessed by a 5-ethynyl-2'-deoxyuridine (EDU) assay and a colony formation assay. Transwell assays were conducted to analyze cell migration and invasion abilities. Cell apoptosis was analyzed by flow cytometry and by using a caspase3 activity assay kit. The glycolysis of NSCLC cells was analyzed using a fluorescence-based glucose/lactate assay kit. A dual-luciferase reporter assay and an RNA pull-down assay were performed to verify the binding relationship between microRNA-582-3p (miR-582-3p) and circ_0002346 or syntaxin-binding protein 6 (STXBP6).

Results

circ_0002346 level was prominently downregulated in NSCLC tissues and cell lines. circ_0002346 overexpression significantly suppressed the proliferation, migration, invasion, and glycolysis and triggered the apoptosis of NSCLC cells. circ_0002346 directly interacted with miR-582-3p, and circ_0002346 overexpression-mediated antitumor effects in NSCLC cells were partly reversed by miR-582-3p overexpression. miR-582-3p directly interacted with the 3' untranslated region (3'UTR) of STXBP6, and STXBP6 silencing partly counteracted circ_0002346 overexpression-mediated antitumor influences in NSCLC cells. circ_0002346 can upregulate the expression of STXBP6 by acting as a miR-582-3p sponge in NSCLC cells. circ_0002346 overexpression suppressed xenograft tumor growth in vivo.

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