Long noncoding RNA GAS5 inhibits metastasis by targeting miR-182/ANGPTL1 in hepatocellular carcinoma

[摘要] Intrahepatic and extrahepatic metastases are responsible for the majority of hepatocellular carcinoma (HCC)-related mortalities. Long noncoding RNAs (lncRNAs) exert important functions in modulating various tumor behaviors. However, the functions and mechanisms of lncRNAs in HCC metastasis remain largely unknown. In this study, downregulation of lncRNA growth arrest-specific 5 (GAS5) was observed in HCC tissues and cells, and predicted poor prognosis of patients with HCC. Through performing gain- and loss-of-function experiments, we found that GAS5 could obviously inhibit migration and invasion of HCC cells in vitro, and suppress tumor metastasis in vivo. Mechanistically, GAS5 functioned as a tumor suppressor in HCC metastasis through directly interacting with miR-182 and abrogating its oncogenic function in this setting. Moreover, GAS5 acted as a competing endogenous RNA (ceRNA) for miR-182 to upregulate the expression of anti-metastasis protein ANGPTL1. Finally, we demonstrated that using ultrasound targeted microbubble destruction (UTMD)-mediated GAS5 transfection could significantly decrease migratory and invasive abilities of HCC cells. Collectively, our study first reveals the mechanism of GAS5/miR-182/ANGPTL1 axis in suppressing HCC metastasis, which provides promising new avenues for therapeutic intervention against HCC progression.

[学科分类] 肿瘤学

[关键词] lncRNA;ceRNA;ANGPTL1;metastasis;HCC