| Hepatocellular carcinoma(HCC)has a high incidence as the top five in the world's top ten malignant tumors.With the gradual spread of hepatitis B virus and the progress of population aging in China,China's new cases of liver cancer account for more than half of the world's total.In theory,liver transplantation can completely remove the primary liver cancer tissue and potential intrahepatic metastases,which is a more effective treatment,but the actual research shows that after the treatment of the disease,the patient has a high probability of tumor recurrence after surgery.It has become the most important factor affecting the long-term survival of patients.Therefore,how to effectively predict and prevent liver cancer recurrence after transplantation has become an urgent need in clinical practice.Further screening for accurate predictive marker molecules for tumor recurrence after transplantation,improving the screening criteria for liver transplant recipients,and developing new anti-tumor recurrence targeted drugs are of great significance for further improving the efficiency of liver transplantation and promoting long-term survival of patients.Aims:Aberrant expression of miR-424 is frequent in a number of malignancys including hepatocellular carcinoma(HCC).Previous studies have demonstrated that miR-424 was down-regulated in HCC tissues and cell lines,and played a suppressive role in the development of HCC.Recent studies revealed that decreased expression of serum miR-424 correlated with poor prognosis of patients with HCC.However,whether miR-424 also play an important role in patients with HCC after liver transplantation(LT)and it has any potential clinical values are poorly known.In the present study,we evaluated the clinical significance of miR-424 expression in predicting tumor recurrence in HCC patients after LT.Methods:Real-time quantitative PCR was used to detect the basal expression level of miR-424 in 6 different hepatocellular carcinoma cell lines and the cancer tissues and paracancerous samples of 121 LT patients in the study.Furthermore,the correlation between miR-424 expressional level and clinical parameters and tumor recurrence were analyzed.At the same time,the lentiviral vector transfection technique was used to simulate the loss and overexpression of miR-424,respectively,and the role of miR-424 in regulating the biological behavior of hepatoma cells was elucidated from both positive and negative aspects.Results:Of the 6 HCC cell lines,HCC-LM3,Huh-7,SMMC-7721,HepG2 and BEL-7402 expressed lower levels of miR-424 than L02(p<0.01).The HCC tissues expressed significantly lower levels of miR-424 than adjacent non-tumorous tissues.Furthermore,LT recipients with recurrent HCC presented lower miR-424 levels than non-recurrent HCC patients(p<0.01).Multivariate analyses revealed that low miR-424 expression was an independent risk factor for HCC recurrence in HCC patients after LT.Patients who no longer met the Milan criteria and exhibited decreased miR-424 expression levels had earlier tumor recurrence following LT.In addition,up-regulation of miR-424 expression significantly reduced the migration,invasiveness and proliferation of HCC cells.Down-regulation of miR-424 in HCC cells significantly promoted the malignant potency of HCC cells.Conclusions:MiR-424 is involved in the regulation of HCC recurrence after LT.Up-regulation of its expression level significantly reduce the ability of HCC cell proliferation,invasion and metastasis and cacinomaregenesis in vivo,and potentially become a precise predictor and a new therapeutic target for recurrent HCC after transplantation. |
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