The novel lncRNA GPC5-AS1 stabilizes GPC5 mRNA by competitively binding with miR-93/106a to suppress gastric cancer cell proliferation

新型 lncRNA GPC5-AS1 通过与 miR-93/106a 竞争性结合来稳定 GPC5 mRNA,从而抑制胃癌细胞增殖

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作者:Guo Bo, Yijie Liu, Wen Li, Lumin Wang, Lingyu Zhao, Dongdong Tong, Lei Ni, Liying Liu, Yannan Qin, Wenjing Wang, Chen Huang

Abstract

Long non-coding RNAs (lncRNAs) are of importance in the genesis and progression of gastric cancer (GC). GPC5-AS1 is a novel lncRNA associated with methyl-CpG-binding protein 2 (MeCP2), identified in our previous microarray analysis; however, the role of GPC5-AS1 in GC remains unknown. In the present study, we demonstrate that GPC5-AS1 is downregulated in GC cells and tissues, and this aberrant expression is regulated by MeCP2 through CpG site binding in the promoter region. Importantly, we also demonstrate that GPC5-AS1 overexpression suppresses cell proliferation, colony formation, and cell cycle transition; induces apoptosis in vitro; and inhibits tumorigenicity in vivo. The expression of the controversial gene GPC5 was downregulated in GC tissues, and elevated GPC5 level could inhibit GC cell growth. Mechanistically, we demonstrated that GPC5-AS1 stabilizes GPC5 mRNA by acting as a molecular sponge for miR-93 and miR-106a, thereby reducing GC tumor progression. In conclusion, our results suggest that GPC5-AS1 may play a pivotal role in GC and serve as a potential diagnostic biomarker and a powerful therapeutic target for GC.

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