The Role Of ANRIL In Occurrence And Development Of Hepatocellular Carcinoma

?Objective?To investigate the expression of antisense non-coding RNA in the INK4 locus(ANRIL)in hepatocellular carcinoma(HCC)tissues and to evaluate its relation to clinicopathological features and prognosis of HCC,at the same to evaluate its influence to liver cancer cell proliferation,apoptosis,migration and invasion.?Methods?A total of 90 patients with primary HCC who underwent a curative liver resection at the Department of hepatobiliary surgery,Wujin hospital affiliated Jiangsu university,and the first affiliated hospital of Nanjing medical university,and the third affiliated hospital of Suzhou university,were included in this study between January 2009and July 2012.Quantitative real-time polymerase chain reaction(qRT-PCR)method was used to detect the expression of ANRIL in liver cancer tissues and adiacent tissues(n=90)and hepatoma cell line.Fisher's exact test were used to analyze its relationship between the expression of ANRIL in HCC tissues and the clinicopathological data.Kaplan-Meier curves and multivariate Cox proportional models were used to study the impact on clinical outcome.Small interfering RNA(siRNA)was used to silence ANRIL.QRT-PCR was used to examine the result of transfection experiment.MTT experiments were used to detect cell cycle and cell apoptosis.scratch tests were used to detect migration ability in vitro.matrigel invasion experiments were used to detect invasion ability in vitro.?Result?ANRIL expression in HCC tissues was significantly higher than in the adjacent non-tumor tissues(t=13.083,P<0.05).The expression of ANRIL was remarkably associated with the histologic grade(?~2=40.724,P<0.05)and TNM stage(?~2=43.245,P<0.05)of HCC patients.In addition,The mean survival time of the patients with high ANRIL was 18.2 months(95%CI:14.9-21.5 months),which was significantly shorter than that of the patients with low ANRIL 39.4 months(95%CI:35.5-43.4months)(?~2=47.590,P<0.05).Multivariate analysis suggested that high ANRIL expression was an independent predictor of poor prognosis(HR=2.143,95%CI:1.083-4.243,P<0.05).QRT-PCR showed that the expression of ANRIL in liver cance cell transfered si-ANRIL was decreased.Moreover,in vitro assays revealed that the decreased expression of ANRIL could suppress the cell proliferation,migration and invasion HCC cells.?Conclusion?ANRIL was high expression in liver cancer,and ANRIL was closely related to TNM stage,pathological grading and the prognosis.ANRIL can obviously promote the liver cancer cell proliferation,migration and invasion ability.ANRIL plays an important role in the development of liver cancer,which can be used as a new clinical tumor markers for judging prognosis and treatment.