circ_0002346 Suppresses Non-Small-Cell Lung Cancer Progression Depending on the Regulation of the miR-582-3p/STXBP6 Axis
Weijie Wang, Yi Lin, Guanghui Zhang, Guofu Shi, Yongsheng Jiang, Wentao Hu, Wei Zuo
Abstract
Background. Accumulating articles have reported the pivotal regulatory roles of circular RNAs (circRNAs) in non-small-cell lung cancer (NSCLC) tumorigenesis. Here, our purpose was to explore the role of circ_0002346 in NSCLC progression and its associated mechanism. Methods. Cell proliferation ability was assessed by a 5-ethynyl-2 <a:math xmlns:a="http://www.w3.org/1998/Math/MathML" id="M1"> <a:msup> <a:mrow/> <a:mrow> <a:mo>′</a:mo> </a:mrow> </a:msup> </a:math> -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 <c:math xmlns:c="http://www.w3.org/1998/Math/MathML" id="M2"> <c:msup> <c:mrow/> <c:mrow> <c:mo>′</c:mo> </c:mrow> </c:msup> </c:math> untranslated region (3 <e:math xmlns:e="http://www.w3.org/1998/Math/MathML" id="M3"> <e:msup> <e:mrow/> <e:mrow> <e:mo>′</e:mo> </e:mrow> </e:msup> </e:math> 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. Conclusion. circ_0002346 overexpression suppressed the malignant properties of NSCLC cells by binding to miR-582-3p to induce the expression of STXBP6.