Abstract
Long non-coding RNAs (lncRNAs) have been suggested as important regulators of cancer development and progression in hepatocellular carcinoma (HCC). Nevertheless, the clinical value and biological roles of LINC00978 in HCC remain unclear. In this study, we detected the expression of LINC00978 in tumor tissues and serum of HCC patients, examined the roles of LINC00978 in HCC progression and elucidated the underlying molecular mechanisms. We found that LINC00978 expression was upregulated in tumor tissues and serum of HCC patients. Higher serum levels of LINC00978 could distinguish HCC patients from hepatitis and liver cirrhosis patients and healthy controls. LINC00978 knockdown inhibited HCC cell proliferation, migration and invasion while promoted cell cycle arrest and apoptosis. Overexpression of LINC00978 led to the opposite effects. LINC00978 knockdown also inhibited HCC growth and metastasis in mouse tumor models. Mechanistically, LINC00978 bound to EZH2 and mediated its accumulation at the promoter region of p21 and E-cadherin genes, leading to the trimethylation of H27K3 and the inhibition of p21 and E-cadherin expression. Moreover, the simultaneous depletion of p21 and E-cadherin expression reversed the inhibitory effects of LINC00978 knockdown on HCC cell proliferation, migration, and invasion. Taken together, these findings suggest that LINC00978 promotes HCC progression by inhibiting p21 and E-cadherin expression via EZH2-mediated epigenetic silencing. LINC00978 may represent a novel biomarker for HCC diagnosis, prognosis, and therapy.
Highlights
Hepatocellular carcinoma (HCC) is one of the most common types of cancers and the third leading cause of cancer-related mortality worldwide[1]
The results showed that LINC00978 expression level was upregulated in HCC tissues compared with the parenchymal normal tissues (Fig. 1a)
The results showed that the expression levels of serum LINC00978 were significantly higher in HCC patients than those in liver benign disease patients and healthy controls, but the expression levels between liver benign disease patients and healthy controls had no statistical difference (Fig. 1d)
Summary
Hepatocellular carcinoma (HCC) is one of the most common types of cancers and the third leading cause of cancer-related mortality worldwide[1]. Long non-coding RNAs (lncRNAs) are a class of transcripts that are more than 200 nt in length[2]. They were initially considered as transcription noise due to their lack of protein-coding capacity, but are thought as important players in human health and diseases. Increasing evidence suggest that lncRNAs are involved in many biological processes of HCC, including initiation, growth, metastasis, and therapy resistance[3,4,5]. DANCR and MUF could increase the stemness features of HCC cells[6,7]. LncTCF7 maintains the ability of liver cancer stem cells to Official journal of the Cell Death Differentiation Association
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