Gene expression profiling of xenografts generated by lung metastasis screening models

Understanding the roles of ncRNAs in tumorigenesis and metastasis would establish avenues for the identification of diagnostic and therapeutic targets. We observed that lncRNA SNHG10 and its derived SCARNA13 were concomitantly upregulated in hepatocellular carcinoma (HCC) pulmonary metastases and associated with poor prognosis. Mechanistically, SCARNA13, modulated by SNHG10, facilitated the cell cycle and epithelial-mesenchymal transition (EMT) of HCC cells by promoting SOX9. 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 through regulating SNHG10 promoter activity, forming a positive feedback loop and continuously stimulating SCARNA13 expression. Our findings characterized a complex epigenetic cause of HCC with clinical implications. To identify ncRNAs involved in HCC metastasis, we grafted Hep3B and SK-Hep1 cells into nude mice and performed a screen of lung metastasis based on orthotopic implanted models in vivo. RNA-seq was conducted to compare the expression profiles between xenografts and parental HCC cells.