3Alpha,7beta-dihydroxy-5beta-cholan-24-oic acid N-(2-sulfoethyl)amide alters the microRNAs expression and promotes cell migration of human hepatocellular carcinoma cells

Abstract

INTRODUCTION: Hepatocellular carcinoma is one of the most malignant cancers with dismal outcomes and the therapeutic strategies remain poor and far from developed. 3alpha,7beta-Dihydroxy-5beta-cholan-24-oic Acid N-(2-Sulfoethyl) amide (Tauroursodeoxycholic Acid, TUDCA) is currently in frequent used for protect the hepatocyte in several kinds of liver disorders including liver cancer. MicroRNA-21 (miR-21) overexpression was reported correlated with the high invasive property of cancer cells. PURPOSE: To profile the microRNA expression alteration in hepatocarcinoma cells with treatment of TUDCA and observe the effect of TUDCA in the invasion and metastasis of hepatocellular carcinoma. Material: Human hepatocellular carcinoma cell line with high metastatic property MHCC97-L. METHODS: We developed a sensitive microRNA on-chip array to detect the miRNAs expression profiling in MHCC97-L cells with or without TUDCA exposure. A quantitative real-time PCR method was introduced to validate the on-chip result. The cell migration was detected by wound healing the invasion chamber assay. Inhibition of miR-21 was conducted by introducing an antisense oligonucleotide complementary to the miRNA. RESULTS: Three microRNAs, let-7f, miR-21 and miR-23a were up-regulated in MHCC97-L with 100 lM TUDCA exposure for 48 hr. The result of the qPCR validates the increase of miR-21 expression in MHCC97-L cells treated with TUDCA comparing with the control. Increased cell migration was observed in MHCC97-L cells with 100 lM TUDCA exposure. Addition of miR-21 inhibitor attenuates the effect of TUDCA on MHCC97-L cell migration.