Clinical significance of C/D box small nucleolar RNA U76 as an oncogene and a prognostic biomarker in hepatocellular carcinoma

Background: Recent evidence has suggested novel roles of small nucleolar RNAs (snoRNAs) in tumorigenicity. However, the roles of C/D box snoRNA U76 (SNORD76) in the development of hepatocellular carcinoma (HCC) remain unknown. Herein, we systematically evaluated dysregulation of snoRNAs in HCC and clarified the biomarker potential and biological significance of SNORD76 in HCC.

Methods: We performed quantitative analyses of the expression of SNORD76 in 66 HCC specimens to compare its expression pattern between tumor tissue and matched non-tumor tissue. The effects of SNORD76 on HCC tumorigenicity were investigated in SK-Hep1 and Huh7 cells as well as in a xenograft nude mouse model.

Results: SNORD76 expression was significantly upregulated in HCC tissues compared to corresponding non-tumor tissues. This upregulation of SNORD76 in HCC tumors was significantly associated with poorer patient survival. Furthermore, inhibiting SNORD76 expression suppressed cell proliferation by inducing G0/G1 cell cycle arrest and apoptosis. Low SNORD76 expression also resulted in decreased HCC growth in an animal model. Conversely, overexpressing SNORD76 promoted cell proliferation. SNORD76 increased HCC cell invasion by inducing epithelial-mesenchymal transition (EMT). Finally, we found that SNORD76 promoted HCC tumorigenicity through activation of the Wnt/β-catenin pathway.

Conclusions: Therefore, we demonstrated for the first time that SNORD76 may function as a novel tumor promoter in HCC and may serve as a promising prognostic biomarker in patients with HCC.