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环状 RNA MAT2B 通过海绵吸附 miR-431 促进非小细胞肺癌细胞的迁移、侵袭和上皮-间充质转化。

Circular RNA MAT2B promotes migration, invasion and epithelial-mesenchymal transition of non-small cell lung cancer cells by sponging miR-431.

机构信息

Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, China.

Department of Respiratory and Critical Care Medicine, Chengdu First People's Hospital, Chengdu, China.

出版信息

Cell Cycle. 2021 Aug;20(16):1617-1627. doi: 10.1080/15384101.2021.1956106. Epub 2021 Jul 21.

Abstract

Circular RNAs (circRNAs) have recently been described as key regulators in the progression of non-small cell lung cancer (NSCLC), and this study aimed to investigate the functional role of circMAT2B in NSCLC. CircMAT2B expression in NSCLC tissues and cell lines was investigated using RT-qPCR analysis. A series of functional experiments, including MTT assay, colony formation assay, wound healing assay and transwell assay, were carried out to investigate the effects of circMAT2B knockdown/overexpression on the malignant traits of NSCLC cells. Western blot analysis was performed to detect the expression of EMT-related proteins. Dual-luciferase reporter assay and RIP assay were further carried out to analyze the interaction between circMAT2B and miR-431 in NSCLC. We observed that circMAT2B was overexpressed in NSCLC tissues and cell lines, and high expression of circMAT2B was closely associated with large tumor size, advanced TNM stage and poor prognosis of NSCLC patients. Further functional experiments showed that circMAT2B knockdown markedly inhibited the proliferation, migration, invasion and EMT of NSCLC cells, whereas circMAT2B overexpression led to the opposing results. Mechanistically, circMAT2B could directly interact with miR-431, and subsequently decrease miR-431 expression in NSCLC. The effects of circMAT2B overexpression in NSCLC cells were abrogated by miR-431 restoration. Our findings revealed the novel oncogenic roles of circMAT2B in NSCLC by sponging miR-431.

摘要

环状 RNA(circRNAs)最近被描述为非小细胞肺癌(NSCLC)进展的关键调节因子,本研究旨在探讨 circMAT2B 在 NSCLC 中的功能作用。使用 RT-qPCR 分析检测 NSCLC 组织和细胞系中的 circMAT2B 表达。进行了一系列功能实验,包括 MTT 分析、集落形成分析、划痕愈合分析和 Transwell 分析,以研究 circMAT2B 敲低/过表达对 NSCLC 细胞恶性特征的影响。Western blot 分析用于检测 EMT 相关蛋白的表达。进一步进行双荧光素酶报告基因检测和 RIP 分析,以分析 NSCLC 中 circMAT2B 与 miR-431 的相互作用。我们观察到 circMAT2B 在 NSCLC 组织和细胞系中过表达,circMAT2B 的高表达与肿瘤体积大、TNM 分期晚和 NSCLC 患者预后不良密切相关。进一步的功能实验表明,circMAT2B 敲低显著抑制 NSCLC 细胞的增殖、迁移、侵袭和 EMT,而 circMAT2B 过表达则导致相反的结果。机制上,circMAT2B 可以直接与 miR-431 相互作用,随后降低 NSCLC 中 miR-431 的表达。circMAT2B 过表达对 NSCLC 细胞的影响被 miR-431 恢复所消除。我们的研究结果揭示了 circMAT2B 通过海绵 miR-431 在 NSCLC 中的新致癌作用。

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