Tumor necrosis factor-α up-regulates the microRNA-21 expression and promotes cell migration in human hepatocellular carcinoma cells MHCC97-L

Abstract

INTRODUCTION: Inflammation of the liver is often observed in the progression of hepatocellular carcinoma. The tumor necrosis factor-a (TNF-a) is one of the major cytokine that may be involved in the inflammation process. microRNA-21 has been reported to play a role in the invasion and metastasis in different kinds of human cancers. PURPOSE: The aim of this study is to involvement of microRNA-21 in the inflammation induced human hepatocellular carcinoma invasion and metastasis in vitro. Material: The human hepatocellular carcinoma cell line with high metastatic property MHCC97-L was used. METHODS: The microRNA expression profile of MHCC97-L upon sustained 10 ng/mL TNF-a exposure was obtained by on-chip microRNA array. The expression of altered microRNAs was validated by quantitative real-time PCR. The cell migration of MHCC97-L cells was measured by wound healing and invasion chamber assay. Inhibition of microRNA-21 was conducted by introducing an antisense oligonucleotide specifically complementary to microRNA-21 into cells. RESULTS: The expression profile of microRNAs in MHCC97-L cells is altered upon 48hr exposure to TNF-a. Up-regulations of microRNA-21, microRNA-146a, microRNA-200b, microRNA-25 and microRNA-29a are observed. The increased expression of microRNA-21 (metastatic related) and microRNA-146a (inflammation related) is validated by qPCR analysis. Increase of cell migration is confirmed in both wound healing assay and invasion chamber assay. Transfection with microRNA-21 antisense oligonucleotide attenuates the migration activity of MHCC97-L induced by TNF-a. CONCLUSION: Exposure of TNF-a could promote the metastatic property of the hepatocellular carcinoma cells MHCC97-L and the over expression of microRNA-21 may play a role.