Long intergenic non-coding RNA Linc00485 promotes lung cancer progression by modulating miR-298/c-Myc axis

长链非编码RNA Linc00485通过调节miR-298/c-Myc轴促进肺癌进展

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作者:Zhenyang Zhang, Wenwei Lin, Yuhan Lin, Mingqiang Kang, Jiafu Zhu, Zhangwei Tong, Long Wu, Jianhai Sun, Jiangbo Lin

Abstract

Long non-coding RNAs (lncRNAs), which are non-protein-coding transcripts, are emerging as novel biomarkers for cancer diagnosis. Their dysregulation is increasingly recognized to contribute to the development and progression of human cancers, including lung cancer. Linc00485 is a newly discovered cancer-related lncRNA; however, little is known about its role in lung cancer progression. In this study, we found that the expression of Linc00485 was significantly increased in human lung cancer tissue and associated with malignant phenotypes, including tumour-node-metastasis (TNM) stage, metastasis and relapse. Furthermore, the proliferative, migratory and invasive abilities of lung cancer cells in vitro were significantly enhanced by overexpression of Linc00485 but inhibited by its silencing. Mechanistically, Linc00485 regulated the expression of c-Myc by directly binding to miR-298; the effects of Linc00485 overexpression could be significantly reversed by a c-Myc inhibitor or small interfering RNA. Xenotransplantation experiments showed that Linc00485 silencing significantly weakened the proliferation potential of A549 cells in vivo. Overall, these findings indicate that Linc00485 overexpression down-regulates miR-298, resulting in the up-regulation of c-Myc and thereby promoting the development of lung cancer.

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