环状RNA_0002346通过调控miR-582-3p/ syntaxin binding protein 6（STXBP6）轴抑制非小细胞肺癌进展
circ_0002346 Suppresses Non-Small-Cell Lung Cancer Progression Depending on the Regulation of the miR-582-3p/STXBP6 Axis.
作者信息
Wang Weijie, Lin Yi, Zhang Guanghui, Shi Guofu, Jiang Yongsheng, Hu Wentao, Zuo Wei
机构信息
Department of Thoracic Surgery, The Affiliated Xiangshan Hospital of Wenzhou Medical University, Ningbo, Zhejiang 315000, China.
Department of Respiration, The Affiliated Xiangshan Hospital of Wenzhou Medical University, Ningbo, Zhejiang 315000, China.
出版信息
Int J Genomics. 2021 Oct 20;2021:1565660. doi: 10.1155/2021/1565660. eCollection 2021.
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'-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 .
CONCLUSION
circ_0002346 overexpression suppressed the malignant properties of NSCLC cells by binding to miR-582-3p to induce the expression of STXBP6.
背景
越来越多的文章报道了环状RNA（circRNA）在非小细胞肺癌（NSCLC）肿瘤发生中的关键调控作用。在此，我们的目的是探讨circ_0002346在NSCLC进展中的作用及其相关机制。
方法
通过5-乙炔基-2'-脱氧尿苷（EDU）检测和集落形成检测评估细胞增殖能力。进行Transwell检测以分析细胞迁移和侵袭能力。通过流式细胞术和使用caspase3活性检测试剂盒分析细胞凋亡。使用基于荧光的葡萄糖/乳酸检测试剂盒分析NSCLC细胞的糖酵解。进行双荧光素酶报告基因检测和RNA下拉检测以验证微小RNA-582-3p（miR-582-3p）与circ_0002346或Syntaxin结合蛋白6（STXBP6）之间的结合关系。
结果
circ_0002346水平在NSCLC组织和细胞系中显著下调。circ_0002346过表达显著抑制NSCLC细胞的增殖、迁移、侵袭和糖酵解，并触发细胞凋亡。circ_0002346直接与miR-582-3p相互作用，并且circ_0002346过表达介导的NSCLC细胞抗肿瘤作用部分被miR-582-3p过表达逆转。miR-582-3p直接与STXBP6的3'非翻译区（3'UTR）相互作用，并且STXBP6沉默部分抵消了circ_0002346过表达介导的NSCLC细胞抗肿瘤影响。circ_0002346可以通过在NSCLC细胞中充当miR-582-3p海绵来上调STXBP6的表达。circ_0002346过表达抑制异种移植肿瘤生长。
结论
circ_0002346过表达通过与miR-582-3p结合以诱导STXBP6表达来抑制NSCLC细胞的恶性特性。
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