环状 RNA circVAPA 通过 miR-342-3p 依赖的 ZEB2 调控促进非小细胞肺癌进展。
Circular RNA circVAPA contributes to non-small-cell lung cancer progression via miR-342-3p-dependent regulation of ZEB2.
机构信息
Department of Respiratory and Critical Care Medicine, Beijing Jishuitan Hospital, No. 31 Xinjiekoudong Street, Xicheng District, Beijing, 100035, China.
出版信息
World J Surg Oncol. 2021 Nov 29;19(1):335. doi: 10.1186/s12957-021-02447-4.
BACKGROUND
Accumulating evidence demonstrated that circular RNAs (circRNAs) play pivotal regulatory roles in the pathology of cancers. Disclosing the roles and molecular mechanisms of circRNAs in tumorigenesis and development is essential to identify novel diagnostic and therapeutic targets. In this study, we explored the role of circVAPA in non-small-cell lung cancer (NSCLC) progression and its associated mechanism.
METHODS
The expression level of RNA was analyzed by real-time quantitative polymerase chain reaction (RT-qPCR). Cell proliferation was assessed by MTT assay and colony-forming assay. Cell apoptosis was analyzed by flow cytometry. Cell migration and invasion were assessed by transwell assays. Dual-luciferase reporter, RNA pull-down, and RNA immunoprecipitation (RIP) assays were used to test the intermolecular interactions. The role of circVAPA was assessed in vivo. And xenograft tumor tissues were analyzed by immunohistochemistry (IHC) staining.
RESULTS
CircVAPA expression was upregulated in NSCLC tissues and cell lines, and a high level of circVAPA was associated with a poor prognosis of NSCLC patients. CircVAPA silencing suppressed the proliferation, migration, and invasion and induced the apoptosis of NSCLC cells. CircVAPA served as a molecular sponge for microRNA-342-3p (miR-342-3p). miR-342-3p interference largely reversed circVAPA knockdown-mediated anti-tumor effects in NSCLC cells. Zinc finger E-box-binding homeobox 2 (ZEB2) was a target of miR-342-3p, and miR-342-3p overexpression suppressed the malignant behaviors of NSCLC cells largely by downregulating ZEB2. CircVAPA silence repressed xenograft tumor growth in vivo, and IHC assay confirmed that circVAPA silence restrained the proliferation and metastasis but induced the apoptosis of NSCLC cells in vivo.
CONCLUSION
CircVAPA contributes to the progression of NSCLC by binding to miR-342-3p to upregulate ZEB2. CircVAPA/miR-342-3p/ZEB2 axis might be a novel potential target for NSCLC treatment.
背景
越来越多的证据表明，环状 RNA（circRNA）在癌症的病理中发挥着关键的调节作用。揭示 circRNA 在肿瘤发生和发展中的作用和分子机制对于识别新的诊断和治疗靶点至关重要。在这项研究中，我们探讨了 circVAPA 在非小细胞肺癌（NSCLC）进展中的作用及其相关机制。
方法
通过实时定量聚合酶链反应（RT-qPCR）分析 RNA 的表达水平。通过 MTT 测定和集落形成测定评估细胞增殖。通过流式细胞术分析细胞凋亡。通过 Transwell 测定评估细胞迁移和侵袭。双荧光素酶报告、RNA 下拉和 RNA 免疫沉淀（RIP）测定用于测试分子间相互作用。在体内评估 circVAPA 的作用。并通过免疫组织化学（IHC）染色分析异种移植肿瘤组织。
结果
circVAPA 在 NSCLC 组织和细胞系中表达上调，高水平的 circVAPA 与 NSCLC 患者的预后不良相关。circVAPA 沉默抑制 NSCLC 细胞的增殖、迁移和侵袭，并诱导细胞凋亡。circVAPA 作为 microRNA-342-3p（miR-342-3p）的分子海绵。miR-342-3p 干扰在很大程度上逆转了 NSCLC 细胞中 circVAPA 敲低介导的抗肿瘤作用。锌指 E 框结合同源盒 2（ZEB2）是 miR-342-3p 的靶标，miR-342-3p 过表达通过下调 ZEB2 显著抑制 NSCLC 细胞的恶性行为。circVAPA 沉默抑制体内异种移植肿瘤的生长，IHC 检测证实 circVAPA 沉默在体内抑制 NSCLC 细胞的增殖和转移，诱导细胞凋亡。
结论
circVAPA 通过与 miR-342-3p 结合来上调 ZEB2，促进 NSCLC 的进展。circVAPA/miR-342-3p/ZEB2 轴可能是 NSCLC 治疗的一个新的潜在靶点。
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