缺氧诱导的lncRNA AC114803在肝细胞癌中的表达及其作用

背景与目的:缺氧是肝细胞癌(HCC)微环境的关键特征之一.缺氧可诱导编码基因和非编码RNA的表达,从而影响HCC的进展.既往研究发现缺氧反应性长链非编码RNA (lncRNA) AC114803与肾细胞癌预后相关,但其在HCC中尚未见研究.因此,本研究探讨HCC中lncRNA-AC114803表达与缺氧的关系及其功能....

Expression of hypoxia-induced long non-coding RNA AC114803 in hepatocellular carcinoma and its function

Background and Aims Hypoxia is one of the key features of microenvironment of hepatocellular carcinoma (HCC). Hypoxia can induce the expressions of coding genes and non-coding RNAs thus, affecting the progression of HCC. Previous studies demonstrated that the hypoxia responsive long non-coding RNA (lncRNA) AC114803 is related to the prognosis of renal cell carcinoma. However, its role in HCC has not been studied. Therefore, this study was performed to investigate the relationship between AC114803 expression and hypoxia and its function in HCC cells.Methods After hypoxia exposure, the hypoxia-regulated lncRNAs in Hep3B cells were detected by lncRNA microarray, and then were verified in HCCLM3 and Hep3B cells by qRT-PCR. The expression of AC114803 in HCC tissues and its relationship with the prognosis of patients were analyzed in TCGA samples. In HCCLM3 and Hep3B cells after transfection with AC114803 overexpression plasmids, the changes in proliferative and migration abilities were determined by CCK-8 assay and wound healing assay, and changes in expressions of the relevant proteins were measured by Western blot analysis.Results LncRNA microarray analysis showed AC114803 was one of the significantly changed lncRNAs in Hep3B cells under hypoxia condition, and qRT-PCR verification showed that only the expression in AC114803 was significantly up-regulated in either HCCLM3 cells or Hep3B cells (all P<0.05). TCGA data analysis showed that the expression of AC114803 in HCC tissues were significantly higher than that in normal liver tissues, and the survival rate in patients with high AC114803 expression was significantly lower than in those with low AC114803 expression (both P<0.05). After AC114803 overexpression, the proliferation and migration abilities of HCC cells (HCCLM3 and Hep3B) were significantly enhanced, and the expressions of the mesenchymal markers N-cadherin and vimentin as well as the anti-apoptotic protein bcl-2 and CCND1 were significantly up-regulated, while the epithelial marker E-cadherin and the pro-apoptotic protein bax were significantly down-regulated (all P<0.05).Conclusion Hypoxia can induce the expression of AC114803 in HCC cells, and high expression of AC114803 is closely associated with the poor prognosis of HCC patients. The action of AC114803 may probably be associated with promoting cell proliferation and migration by regulating the epithelial-mesenchymal transition process.