Abstract
Hepatocellular carcinoma (HCC) has become one of the most common leading causes of cancer-related deaths worldwide. This study investigates the role of lncRNA, SPRY4-IT1 in the development of HCC. Quantitative real-time PCR (qRT-PCR) was performed and the results showed that SPRY4-IT1 expression was up-regulated in HCC tissues and high expression of SPRY4-IT1 was associated with poor 5-year overall survival in the HCC patient cohort. Clinicopathological analysis showed that the expression of SPRY4-IT1 was significantly correlated with TNM stage in HCC patients. In vitro CCK-8 assay, colony formation assay, cell invasion and migration assays demonstrated that knock-down of SPRY4-IT1 suppressed cell proliferation, colony formation, cell invasion and migration in HCC cells. Flow cytometric analysis showed that knock-down of SPRY4-IT1 induced cell cycle arrest at G0/G1 phase and induced apoptosis. In addition, knock-down of SPRY4-IT1 also suppressed the mRNA and protein expression of estrogen-related receptor α (ERRα). Similarly, knock-down of ERRα inhibited cell proliferation, colony formation, cell invasion and migration in HCC cells. More importantly, ERRα overexpression antagonized the effects of SPRY4-IT1 knock-down on cell proliferation, colony formation, cell invasion and migration in HCC cells. Taken together, our data highlights the pivotal role of SPRY4-IT1 in the tumorigenesis of HCC.
Highlights
Hepatocellular carcinoma (HCC) has become one of the most common leading causes of cancer-related deaths worldwide[1]
We found that the expression of SPRY4-IT1 in HCC tissues were significantly higher than that examined in the respective adjacent normal non-cancerous liver tissues (Fig. 1A, P < 0.001)
The results showed that high level of SPRY4-IT1 was significantly correlated with poor 5-year overall survival rate in HCC patients (Fig. 1B, P < 0.05)
Summary
Hepatocellular carcinoma (HCC) has become one of the most common leading causes of cancer-related deaths worldwide[1]. The high mortality and poor prognosis of HCC are attributed to the incomplete understanding of the molecular mechanisms underlying the development and progression of HCC. In this regard, further understanding the molecular mechanisms is of great clinical significance for developing novel therapeutic targets for HCC treatment. In HCC, an increasing number of lncRNAs have been reported to be associated with cancer development. The expression of lncRNA, SPRY4 intronic transcript 1 (SPRY4-IT1), transcribed from an intron, is found to be up-regulated in various types of cancers including www.nature.com/scientificreports/. ERRα has been suggested to be associated with the development and progression of various types of cancers. Whether ERRα plays a role in HCC development is still unclear
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