Long Noncoding RNA GAS5 Suppresses Tumorigenesis by Inhibiting miR-23a Expression in Non-Small Cell Lung Cancer

• Published in: Oncology research 2017-07, Vol.25 (6), p.1027-1037
• Main Authors: Mei, Yongcheng, Si, Jinchun, Wang, Yun, Huang, Zhuangshi, Zhu, Haiwen, Feng, Shijun, Wu, Xuezhi, Wu, Liwen
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Apoptosis - genetics; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - pathology; Cell Line, Tumor; Cell Proliferation - genetics; Down-Regulation - genetics; Gas5; Gene Expression Regulation, Neoplastic; Humans; Invasion; Long Noncoding Rna (lncrna); Lung Neoplasms - genetics; Lung Neoplasms - pathology; Male; Mice, Inbred BALB C; Mice, Nude; MicroRNAs - genetics; Mir-23a; Non-Small Cell Lung Cancer (nsclc); Proliferation; RNA, Long Noncoding - genetics; Up-Regulation - genetics
• ISSN: 0965-0407; 1555-3906
• DOI: 10.3727/096504016X14822800040451

Previous studies reported that elevated expression of long noncoding RNA (lncRNA) GAS5 led to the arrest of non-small cell lung cancer (NSCLC) cell growth and a promotion of apoptosis both in vitro and in vivo. However, its underlying molecular mechanism in NSCLC is still unclear. In the present study, we noted that GAS5 was downregulated in NSCLC tissues and cells and was negatively correlated with miR-23a expression. Luciferase reporter assay and qRT-PCR analysis demonstrated that GAS5 directly interacted with miR-23a and reversely regulated its expression. miR-23a overexpression markedly promoted NSCLC cell proliferation and invasion, while GAS5 overexpression dramatically inhibited NSCLC cell proliferation and invasion and promoted apoptosis. Functional analysis indicated that miR-23a overexpression significantly abolished GAS5 overexpression-induced inhibition of proliferation and invasion, as well as promotion of apoptosis in NSCLC cells. Moreover, xenograft experiments further revealed that upregulation of GAS5 notably impaired the growth of transplanted tumors by suppressing miR-23a in nude mice. These results suggested that overexpression of lncRNA GAS5 inhibits tumorigenesis of NSCLC by inhibiting miR-23a in vitro and in vivo, providing a potential therapeutic strategy for patients with NSCLC.