Department of Respiratory Medicine, Jinling Hospital, Second Military Medical University, Nanjing, China.
Cancer Med. 2020 Feb;9(3):1196-1208. doi: 10.1002/cam4.2776. Epub 2019 Dec 20.
According to the global cancer statistic, lung cancer is one of the most dangerous tumors, which poses a serious threat to human health. Exploration the mechanism of lung cancer and new targeted therapeutic measures is always the hot topic. Long noncoding RNA (lncRNA) is an important factor affecting the development of tumors. However, the research on the mechanism of lncRNA in the progress of lung cancer needs to be further expanded. In this study, we found that the expression of lncRNA GMDS-AS1 was significantly reduced in lung adenocarcinoma (LUAD) tissues and cells. Upregulated GMDS-AS1 can significantly inhibit the proliferation of LUAD cells and promote cell apoptosis in vitro and in vivo. The results indicate that GMDS-AS1 acts as a tumor suppressor gene to affect the development of LUAD. Further studies revealed that GMDS-AS1 is a target gene of miR-96-5p, and GMDS-AS1 regulates proliferation and apoptosis of LUAD cells in association with miR-96-5p. In addition, we also confirmed that CYLD lysine 63 deubiquitinase (CYLD) is also a target gene of miR-96-5p. Through various validations, we confirmed that GMDS-AS1 can act as a ceRNA to upregulate the expression of CYLD by sponging miR-96-5p. Moreover, the intervention of GMDS-AS1/miR-96-5p/CYLD network can regulate the proliferation and apoptosis of LUAD cells. In this study, we revealed that the GMDS-AS1/miR-96-5p/CYLD network based on ceRNA mechanism plays an important role in the development of LUAD and provides a new direction and theoretical basis for targeted therapy of LUAD.
根据全球癌症统计数据，肺癌是最危险的肿瘤之一，对人类健康构成严重威胁。探索肺癌的机制和新的靶向治疗措施一直是热门话题。长链非编码 RNA（lncRNA）是影响肿瘤发展的重要因素。然而，lncRNA 在肺癌进展中的机制研究有待进一步拓展。在本研究中，我们发现 lncRNA GMDS-AS1 在肺腺癌（LUAD）组织和细胞中的表达显著降低。上调 GMDS-AS1 可显著抑制 LUAD 细胞的增殖，并在体外和体内促进细胞凋亡。结果表明 GMDS-AS1 作为一种肿瘤抑制基因影响 LUAD 的发展。进一步的研究表明 GMDS-AS1 是 miR-96-5p 的靶基因，GMDS-AS1 通过与 miR-96-5p 共同调节 LUAD 细胞的增殖和凋亡。此外，我们还证实 CYLD 赖氨酸 63 去泛素化酶（CYLD）也是 miR-96-5p 的靶基因。通过各种验证，我们证实 GMDS-AS1 可以作为 ceRNA 通过海绵 miR-96-5p 来上调 CYLD 的表达。此外，GMDS-AS1/miR-96-5p/CYLD 网络的干预可以调节 LUAD 细胞的增殖和凋亡。在本研究中，我们揭示了基于 ceRNA 机制的 GMDS-AS1/miR-96-5p/CYLD 网络在 LUAD 的发展中起重要作用，并为 LUAD 的靶向治疗提供了新的方向和理论依据。
