Abstract
Recent studies show that small nucleolar RNAs (snoRNAs) play an important role in tumorigenesis. SNORA42 is a potential therapeutic target and prognostic biomarker for various cancers, and the aim of the present study was to investigate the function and clinical relevance of SNORA42 in hepatocellular carcinoma (HCC). We detected the expression levels of SNORA42 in HCC and normal liver tissue samples, as well as in tumor and hepatocyte-derived cell lines. SNORA42 was significantly upregulated in the HCC tissues and cells compared to the adjacent liver tissues and normal hepatocytes. Furthermore, overexpression of SNORA42 correlated with poor prognosis in the HCC patients. Knocking down SNORA42 in HCC cell lines decreased their proliferation, migration and invasion in vitro, and inhibited tumor growth and metastasis in vivo. In contrast, ectopic expression of SNORA42 promoted HCC cell proliferation and inhibited apoptosis. Mechanistically, SNORA42 exerted its oncogenic effects by targeting the p53 signaling pathway and cell cycle transition. In conclusion, SNORA42 acted as an oncogene in HCC and was a potential prognostic biomarker and therapeutic target.
Highlights
Hepatocellular carcinoma (HCC) ranks second in terms of tumorrelated deaths and disability-adjusted life years (DALYs) worldwide [1, 2]
Consistent with the patient data, SNORA42 was upregulated in all HCC cell lines compared to the immortalized human liver cell line HL-7702 (Fig. 1b), and the expression levels were high in the HCCLM9 (11.75 ± 0.8764, *p = 0.0002) and SK-Hep1 (5.000 ± 0.8238, *p = 0.0037) cells
SNORA42 promoted the malignant behavior of HCC cells by inhibiting the p53 pathway We identified over 70 differentially expressed genes (DEGs) in the SNORA42-knockdown HCCLM9 and SK-Hep1 cells relative to the DISCUSSION Liver cancer is a highly invasive malignancy associated with considerable socio-economic burden worldwide [10]
Summary
Hepatocellular carcinoma (HCC) ranks second in terms of tumorrelated deaths and disability-adjusted life years (DALYs) worldwide [1, 2]. Since the early stage of HCC is asymptomatic, most patients are initially diagnosed in the advanced stage, which precludes radical surgery [4]. It is crucial to identify novel biomarkers for the early diagnosis and treatment of liver cancer. SNORA42 is highly expressed in nonsmall-cell lung cancer (NSCLC) tissues and correlates with poor patient prognosis. It has an oncogenic role in colorectal cancer (CRC), and has been established as a prognostic marker of prostate cancer [6,7,8,9]. Only few snoRNAs that are potentially associated with HCC have been identified so far, and the molecular mechanisms underlying its tumorigenic actions are largely unknown
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