Abstract
Hepatocellular carcinoma (HCC) is a common malignancy with a poor prognosis. Therefore, there is an urgent call for the investigation of novel biomarkers in HCC. In the present study, we identified 6 upregulated lncRNAs in HCC, including LINC01134, RHPN1-AS1, NRAV, CMB9-22P13.1, MKLN1-AS, and MAPKAPK5-AS1. Higher expression of these lncRNAs was correlated to a more advanced cancer stage and a poorer prognosis in HCC patients. Enrichment analysis revealed that these lncRNAs played a crucial role in HCC progression, possibly through a series of cancer-related biological processes, such as cell cycle, DNA replication, histone acetyltransferase complex, fatty acid oxidation, and lipid modification. Moreover, competing endogenous RNA (ceRNA) network analysis revealed that these lncRNAs could bind to certain miRNAs to promote HCC progression. Loss-of-function assays indicated that silencing of RHPN1-AS1 significantly suppressed HCC proliferation and migration. Though further validations are still needed, these identified lncRNAs could serve as valuable potential biomarkers for HCC prognosis.
Highlights
Hepatocellular carcinoma (HCC) has ranked as the second leading cause of cancer-related deaths worldwide [1], as more than 782,000 HCC-associated deaths are predicted to occur annually [2]
(a), these long noncoding RNAs (lncRNAs) had significantly higher expression levels in HCC tissues than in nontumor tissues. Survival analysis of these lncRNAs revealed that 15 lncRNAs, including CTB147N14.6, RP11-286H15.1, RP11-295D4.1, RHPN1-AS1, SNRPEP2, LINC01134, NRAV, NAP1L1P1, CMB922P13.1, MKLN1-AS, RP5-864K19.4, CTC-297N7.9, MAPKAPK5-AS1, MIR210HG, and AP001469.9, were closely associated with overall survival (OS) time of patients with hepatocellular carcinoma (Figure 1(b), log-rank test, P value < 0.05)
Survival analysis was conducted to identify lncRNAs associated with disease-free survival (DFS)
Summary
Hepatocellular carcinoma (HCC) has ranked as the second leading cause of cancer-related deaths worldwide [1], as more than 782,000 HCC-associated deaths are predicted to occur annually [2]. ID1 enhanced tumor growth in HCC patients [3], while FABP4 inhibited tumor growth and invasion [4]. Noncoding RNAs (ncRNAs) have emerged as a very promising resource for the identification of prognostic biomarkers. XIST [7,8,9] and LINC01138 [10] were reported to link to the regulation of HCC growth and metastasis. LncRNA XIST regulates HCC tumor growth and migration by sponging miR-497-5p [9]. Several lncRNAs have been demonstrated as potential prognostic biomarkers in HCC. Overexpression of lncRNA ENST00000429227.1, LINC00511, SNHG16, and AK001796 were associated with worse prognosis in HCC patients [12]. A further appreciation of the molecular functions and expression patterns of lncRNAs could help reveal novel biomarkers for HCC
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