Small nucleolar RNAs (snoRNAs) as a novel molecular species may have significant and comprehensive influences on the development and progression of hepatocellular carcinoma (HCC). We recently characterized snoRNA transcriptome signatures in HCC tissues by small RNA sequencing and found that small nucleolar RNA 78 (SNORD78) was associated with HCC. However, little is known about the pathological role of SNORD78 in HCC patients. This study aimed to profile SNORD78 expression signature and then to explore the pathogenesis of SNORD78 in HCC. The real-time PCR results showed that SNORD78 was greatly upregulated in HCC tissues than adjacent noncancerous tissues (p = 0.004). Correlation analysis showed that high-level expression of SNORD78 was notably associated with tumor number (single vs. multiply, p = 0.02), stage (I∼II vs. III∼IV, p = 0.014), and distant metastasis (absent vs. present, p = 0.01) in HCC patients. Univatiate and multivariate analyses showed that SNORD78 was a significant prognostic predictor for overall survival and recurrence-free survival of HCC patients (hazard ratio = 1.375, 95 % CI = 1.125–1.680, p = 0.002; hazard ratio = 1.418, 95 % CI = 1.201–1.675, p < 0.001). Moreover, Kaplan-Meier analysis showed that high-level expression of SNORD78 was associated with short overall survival and recurrence-free survival of HCC patients (p = 0.023, 0.014). Functionally, knockdown of SNORD78 significantly inhibited cellular proliferation, migration, and invasion of SK-Hep-1 via inducing G0/G1 cell cycle arrest and apoptosis. In conclusion, SNORD78 may be associated with aggressive phenotype and poor prognosis of HCC.
Small nucleolar RNA SNORD78 Hepatocellular carcinoma Progression Progniosis
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This study was funded by the National Basic Research Program of China (973 Program) (2012CB720600, 2012CB720605).
Compliance with ethical standards
The study was approved by the medical ethical committee of Zhongnan Hospital of Wuhan University. All participants were Han population from China, who gave their informed written consent.
Poh Z, Shen L, Yang HI, Seto WK, Wong VW, Lin CY, et al. Real-world risk score for hepatocellular carcinoma (RWS-HCC): a clinically practical risk predictor for HCC in chronic hepatitis B. Gut. 2016;65:887–8.CrossRefPubMedGoogle Scholar
D’Anzeo M, Faloppi L, Scartozzi M, Giampieri R, Bianconi M, Del PM, et al. The role of micro-RNAs in hepatocellular carcinoma: from molecular biology to treatment. Molecules. 2014;19:6393–406.CrossRefPubMedGoogle Scholar
Thorenoor N, Slaby O. Small nucleolar RNAs functioning and potential roles in cancer. Tumour Biol. 2015;36:41–53.CrossRefPubMedGoogle Scholar
Matera AG, Terns RM, Terns MP, Non-coding RNA. Lessons from the small nuclear and small nucleolar RNAs. Nat Rev Mol Cell Biol. 2007;8:209–20.CrossRefPubMedGoogle Scholar
Badhai J, Frojmark AS, DE J, Schuster J, Dahl N. Ribosomal protein S19 and S24 insufficiency cause distinct cell cycle defects in Diamond-Blackfan anemia. Biochim Biophys Acta. 2009;1792:1036–42.CrossRefPubMedPubMedCentralGoogle Scholar
Hariharan N, Sussman MA. Stressing on the nucleolus in cardiovascular disease. Biochim Biophys Acta. 2014;1842:798–801.CrossRefPubMedGoogle Scholar
Trainor PA, Merrill AE. Ribosome biogenesis in skeletal development and the pathogenesis of skeletal disorders. Biochim Biophys Acta. 2014;1842:769–78.CrossRefPubMedGoogle Scholar
Tanaka R, Satoh H, Moriyama M, Satoh K, Morishita Y, Yoshida S, et al. Intronic U50 small-nucleolar-RNA (snoRNA) host gene of no protein-coding potential is mapped at the chromosome breakpoint t(3;6)(q27;q15) of human B-cell lymphoma. Genes Cells. 2000;5:277–87.CrossRefPubMedGoogle Scholar
Mei YP, Liao JP, Shen J, Yu L, Liu BL, Liu L, et al. Small nucleolar RNA 42 acts as an oncogene in lung tumorigenesis. Oncogene. 2012;31:2794–804.CrossRefPubMedGoogle Scholar
Zheng D, Zhang J, Ni J, Luo J, Wang J, Tang L, et al. Small nucleolar RNA 78 promotes the tumorigenesis in non-small cell lung cancer. J Exp Clin Cancer Res. 2015;34:49.CrossRefPubMedPubMedCentralGoogle Scholar
Su J, Liao J, Gao L, Shen J, Guarnera MA, Zhan M, et al. Analysis of small nucleolar RNAs in sputum for lung cancer diagnosis. Oncotarget. 2016;7:5131–42.PubMedGoogle Scholar
Sun M, Jin FY, Xia R, Kong R, Li JH, TP X, et al. Decreased expression of long noncoding RNA GAS5 indicates a poor prognosis and promotes cell proliferation in gastric cancer. BMC Cancer. 2014;14:319.CrossRefPubMedPubMedCentralGoogle Scholar
Shi X, Sun M, Liu H, Yao Y, Kong R, Chen F, et al. A critical role for the long non-coding RNA GAS5 in proliferation and apoptosis in non-small-cell lung cancer. Mol Carcinog. 2015;54(Suppl 1):E1–E12.CrossRefPubMedGoogle Scholar
Yin D, He X, Zhang E, Kong R, De W, Zhang Z. Long noncoding RNA GAS5 affects cell proliferation and predicts a poor prognosis in patients with colorectal cancer. Med Oncol. 2014;31:253.CrossRefPubMedGoogle Scholar
Schneider C, King RM, Philipson L. Genes specifically expressed at growth arrest of mammalian cells. Cell. 1988;54:787–93.CrossRefPubMedGoogle Scholar
ZQ T, Li RJ, Mei JZ, Li XH. Down-regulation of long non-coding RNA GAS5 is associated with the prognosis of hepatocellular carcinoma. Int J Clin Exp Pathol. 2014;7:4303–9.Google Scholar
Giakoustidis A, Giakoustidis D, Mudan S, Sklavos A, Williams R. Molecular signalling in hepatocellular carcinoma: role of and crosstalk among WNT/ss-catenin, Sonic Hedgehog, Notch and Dickkopf-1. Can J Gastroenterol Hepatol. 2015;29:209–17.CrossRefPubMedPubMedCentralGoogle Scholar
Su H, Xu T, Ganapathy S, Shadfan M, Long M, Huang TH, et al. Elevated snoRNA biogenesis is essential in breast cancer. Oncogene. 2014;33:1348–58.CrossRefPubMedGoogle Scholar
Donati G, Bertoni S, Brighenti E, Vici M, Trere D, Volarevic S, et al. The balance between rRNA and ribosomal protein synthesis up- and downregulates the tumour suppressor p53 in mammalian cells. Oncogene. 2011;30:3274–88.CrossRefPubMedGoogle Scholar