Xu Zhe-Yuan, Peng Jun, Shi Zhi-Zhou, Chen Xin-Long, Cheng Hong-Zhong, Wang Han, Wang Yang, Wang Guo-Ping, Jiang Wen, Peng Hao
Department of Thoracic Surgery, The First People's Hospital of Yunnan Province, Kunming, Yunnan, P.R. China.
Medical School, Kunming University of Science and Technology, Kunming, Yunnan, P.R. China.
Biochem Cell Biol. 2021 Jun;99(3):330-338. doi: 10.1139/bcb-2019-0396. Epub 2020 Oct 27.
Lung cancer is the most common cause of cancer-related death in the world. Long non-coding RNAs (lncRNAs) are longer than 200 nucleotide transcripts, and are not translated into protein. The lncRNA linc00662 is overexpressed in lung cancer; however, its role in lung cancer is still unknown. In our study, by analyzing the TCGA data, we found that linc00662 was overexpressed in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). We knocked-down the expression of linc00662 using siRNA, and found that silencing linc00662 significantly inhibited the proliferation and colony formation of the lung cancer cell lines A549 and H460. We also found that knockdown of linc00662 increased the expression of the microRNA miR-145-5p and decreased the expression of the () gene. We further show that linc00662 binds with miR-145-5p, and that miR-145-5p binds to the 3'UTR of PAFAH1B2. miR-145-5p negatively regulates PAFAH1B2 both at the mRNA and the protein level. Loss of miR-145-5p abolished the inhibitory effects of silencing linc00662 on the proliferation and colony formation of A549 and H460 cells. These findings indicate that linc00662 functions as an oncogene by acting as a competing endogenous RNA (ceRNA) and sponges and regulates miR-145-5p in lung cancer, and thus may provide a potential target for treating lung cancer.
肺癌是全球癌症相关死亡的最常见原因。长链非编码RNA（lncRNAs）是长度超过200个核苷酸的转录本，不翻译成蛋白质。lncRNA linc00662在肺癌中过表达；然而，其在肺癌中的作用仍不清楚。在我们的研究中，通过分析TCGA数据，我们发现linc00662在肺腺癌（LUAD）和肺鳞状细胞癌（LUSC）中过表达。我们使用siRNA敲低linc00662的表达，发现沉默linc00662显著抑制肺癌细胞系A549和H460的增殖和集落形成。我们还发现敲低linc00662增加了微小RNA miR-145-5p的表达并降低了（）基因的表达。我们进一步表明linc00662与miR-145-5p结合，并且miR-145-5p与PAFAH1B2的3'UTR结合。miR-145-5p在mRNA和蛋白质水平上均负调控PAFAH1B2。miR-145-5p的缺失消除了沉默linc00662对A549和H460细胞增殖和集落形成的抑制作用。这些发现表明linc00662通过作为竞争性内源性RNA（ceRNA）发挥作用，在肺癌中充当海绵并调节miR-145-5p，因此可能为治疗肺癌提供潜在靶点。
