LncRNA SNHG10 Facilitates Hepatocarcinogenesis and Metastasis by Modulating Its Homolog SCARNA13 via a Positive Feedback Loop

摘要

Understanding the roles of noncoding RNAs (ncRNA) in tumorigenesis and metastasis would establish novel avenues to identify diagnostic and therapeutic targets. Here, we aimed to identify hepatocellular carcinoma (HCC)-specific ncRNA and to investigate their roles in hepatocarcinogenesis and metastasis. RNA-seq of xenografts generated by lung metastasis identified long noncoding RNA small nucleolar RNA host gene 10 (SNHG10) and its homolog SCARNA13 as novel drivers for the development and metastasis of HCC. SNHG10 expression positively correlated with SCARNA13 expression in 64 HCC cases, and high expression of SNHG10 or SCARNA13 was associated with poor overall survival. As SCARNA13 showed significant rise and decline after overexpression and knockdown of SNHG10, respectively, we hypothesized that SNHG10 might act as an upstream regulator of SCARNA13. SNHG10 and SCARNA13 coordinately contributed to the malignant phenotype of HCC cells, where SNHG10 served as a sponge for miR-150-5p and interacted with RPL4 mRNA to increase the expression and activity of c-Myb. Reciprocally, upregulated and hyperactivated c-Myb enhanced SNHG10 and SCARNA13 expression by regulating SNHG10 promoter activity, forming a positive feedback loop and continuously stimulating SCARNA13 expression. SCARNA13 mediated SNHG10-driven HCC cell proliferation, invasion, and migration and facilitated the cell cycle and epithelial-mesenchymal transition of HCC cells by regulating SOX9. Overall, we identified a complex circuitry underlying the concomitant upregulation of SNHG10 and its homolog SCARNA13 in HCC in the process of hepatocarcinogenesis and metastasis.