The long non-coding RNA colon cancer-associated transcript 1 (CCAT1) has been investigated to involve in the progression of non-small cell lung cancer (NSCLC). Thus, this study aims to explore the detailed molecular mechanisms of CCAT1 in NSCLC. The expression of CCAT1, miR-216a-5p, RAP2B, Bax, Bcl-2, and cleaved caspase 3 was detected by qRT-PCR or Western blot. Cell proliferation, apoptosis, migration, and invasion were analyzed using cell counting kit-8, flow cytometry or Transwell assays, respectively. The interaction between miR-216a-5p and CCAT1 or RAP2B was analyzed by luciferase reporter, RNA immunoprecipitation, and pull-down assays. The expression of CCAT1 was elevated in NSCLC, and CCAT1 deletion could inhibit NSCLC cell proliferation, migration, and invasion but induce apoptosis in vitro as well as imped tumor growth in vivo. MiR-216a-5p was confirmed to be a target of CCAT1, and silencing miR-216a-5p could reverse CCAT1 depletion-mediated inhibitory effects on cell tumorigenesis in NSCLC. Besides that, miR-216a-5p was decreased in NSCLC, and miR-216a-5p restoration inhibited cell tumorigenesis by regulating RAP2B, which was verified to be a target of miR-216a-5p. Additionally, co-expression analysis suggested that CCAT1 indirectly regulated RAP2B level by targeting miR-216a-5p in NSCLC cells. Taken together, CCAT1 deletion could inhibit cell progression in NSCLC through miR-216a-5p/RAP2B axis, indicating a novel pathway underlying NSCLC cell progression and providing new potential targets for NSCLC treatment.

Impact statement

We investigated that CCAT1 expression was elevated in NSCLC and CCAT1 deletion was identified to inhibit cell carcinogenic phenotypes in NSCLC cells via miR-216a-5p/RAP2B axis, which reveals a novel pathway underlying progression in NSCLC cells and providing potential targets for NSCLC treatment.

中文翻译：

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长非编码RNA CCAT1通过调节miR-216a-5p/RAP2B轴促进非小细胞肺癌进展

长链非编码 RNA 结肠癌相关转录物 1 (CCAT1) 已被研究参与非小细胞肺癌 (NSCLC) 的进展。因此，本研究旨在探讨CCAT1在NSCLC中的详细分子机制。通过qRT-PCR或Western blot检测CCAT1、miR-216a-5p、RAP2B、Bax、Bcl-2和cleaved caspase 3的表达。分别使用细胞计数试剂盒8、流式细胞术或Transwell 分析细胞增殖、凋亡、迁移和侵袭。通过荧光素酶报告基因、RNA 免疫沉淀和 Pull-down 测定分析 miR-216a-5p 与 CCAT1 或 RAP2B 之间的相互作用。 CCAT1在NSCLC中表达升高，CCAT1缺失可以抑制NSCLC细胞的增殖、迁移和侵袭，但在体外诱导细胞凋亡，并在体内阻碍肿瘤生长。 miR-216a-5p 被证实是 CCAT1 的靶标，沉默 miR-216a-5p 可以逆转 CCAT1 耗竭介导的对 NSCLC 细胞肿瘤发生的抑制作用。此外，miR-216a-5p在NSCLC中减少，miR-216a-5p恢复通过调节RAP2B抑制细胞肿瘤发生，RAP2B被证实是miR-216a-5p的靶标。此外，共表达分析表明 CCAT1 通过靶向 NSCLC 细胞中的 miR-216a-5p 间接调节 RAP2B 水平。综上所述，CCAT1缺失可以通过miR-216a-5p/RAP2B轴抑制NSCLC细胞进展，表明NSCLC细胞进展的新途径，并为NSCLC治疗提供新的潜在靶点。

 影响报告

我们研究了 NSCLC 中 CCAT1 表达升高，并且发现 CCAT1 缺失可通过 miR-216a-5p/RAP2B 轴抑制 NSCLC 细胞中的细胞致癌表型，这揭示了 NSCLC 细胞进展的新途径，并为 NSCLC 治疗提供了潜在靶标。