Identification of pathogenesis-related microRNAs in hepatocellular carcinoma by expression profiling

Abstract

Abstract. Hepatocellular carcinoma (HCC) is one of the most common malignant tumors of the liver. Since postoperative recurrence and intrahepatic metastases occur frequently, the postoperative 5-year survival rate is low. To investigate the molecular mechanisms of HCC progression, mRNA as well as microRNA (miRNA) expression levels have been profiled in various studies. However, no previous study has comprehensively compared the expression of miRNAs in HCC patients with various clinical features using the tumor and surrounding non-tumor tissues and normal liver samples. In this study, we profiled the expression of miRNAs in tumor and non-tumor tissues from 40 HCC patients with heterogeneous pathogenesis and 6 surrounding non-tumor tissues from patients with metastatic liver cancer. To identify miRNAs specific to each disease state, we comprehensively compared the expression of miRNAs in various combinations. The results indicate that the expression of many known as well as novel miRNAs was altered in patients with the hepatitis C virus infection compared with those with the hepatitis B virus and without any virus infection. The following miRNAs were downregulated in the tumor and non-tumor tissues, and thus could serve as novel biomarkers for chronic liver diseases: miR-18b*, miR-296-5p, miR-557, miR-581, miR-625*, miR-1228, miR-1249 and miR-2116*. Similarly, miR-129*, miR-146b-3p and miR-448 are novel candidates for HCC biomarkers regardless of virus infection.

miR-448 downregulates MPPED2 to promote cancer proliferation and inhibit apoptosis in oral squamous cell carcinoma

“…It is upregulated in breast cancer (24) and early cerebral aneurysm (12), and downregulated in hepatocellular carcinoma (25) . It has also been reported that miR-448 is the most downregulated microRNA following chemotherapy in breast cancer (13), suggesting that it may act as an oncogene or anti-oncogene in different cancers.…”

MicroRNA-129 in Human Cancers: from Tumorigenesis to Clinical Treatment

“…Since the level of VCP and miR-129-5p in HCC samples was significantly distinctive from that in adjacent normal tissues, the two molecules may be novel indicators for prediction of the genesis of HCC. Katayama et al referred miR-129 as a novel candidate for HCC biomarkers regardless of virus infection [92]. Additionally, a negative correlation between miR-129-5p expression levels and ETS1 levels was reported in HCC tissues, suggesting that miR-129-5p could be a helpful prognostic marker and/or therapeutic target in HCC [77].…”

MicroRNA expression profiling in patients with hepatocellular carcinoma of familial aggregation and hepatitis B virus infection

“…Since miRNAs perform important roles in various pivotal biological processes, dysregulated miRNA expression has been implicated in a variety of human diseases, including chronic HBV infection and hepatocarcinogenesis (19). An increasing amount of evidence has indicated that dysregulation of miRNAs has important roles in HBV infection and HBV-associated HCC (9,(20)(21)(22). Numerous studies have demonstrated that the HBx protein is associated with the regulation of miRNAs, which affects basic tumor processes, including cellular proliferation, differentiation and metastasis (12,(23)(24)(25)(26)(27).…”