Original ArticleUpregulation of SNHG6 regulates ZEB1 expression by competitively binding miR-101-3p and interacting with UPF1 in hepatocellular carcinoma

- SNHG6 promotes proliferation, invasion and migration in HCC.
- SNHG6 acts as a competing endogenous RNA and regulates ZEB1 expression by competitively binding miR-101-3p.
- SNHG6 induces EMT by increasing ZEB1-mediated MMP-2/9 expression in HCC.
- SNHG6 activates the TGF-β/Smad pathway by binding UPF1.

Emerging evidence suggests that small nucleolar RNAs (snoRNAs) and their host genes (SNHGs) have malfunctioning roles in the development of human cancers. We globally investigated the molecular mechanisms by which snoRNA host gene 6 (SNHG6) promotes hepatocellular carcinoma (HCC) progression using human tissues and cell lines. We found that SNHG6 is overexpressed in HCC tissues and in hepatoma cell lines and is closely associated with histologic grade, hepatitis B virus DNA, Barcelona Clinic Liver Cancer stage and portal vein tumor thrombus in patients with HCC. Knockdown of SNHG6 induced apoptosis and repressed cell cycle progression in hepatoma cell lines, whereas transgenic expression of SNHG6 in the immortalized human hepatic cell line L02 had opposite effects. Xenograft tumors grown from SNHG6-knockdown cells had smaller mean volumes than did tumors grown from control cells. SNHG6 may act as a competing endogenous RNA, effectively becoming a sink for miR-101-3p and thereby modulating the derepression of zinc finger E-box binding homeobox 1, imposing an additional level of post-transcriptional regulation. Functionally, SNHG6 promotes tumor growth and metastasis by inducing epithelial to mesenchymal transition. Further investigations showed that SNHG6 could affect HCC tumorigenesis by binding to up-frameshift protein 1 and regulating Smad7 expression.