Abstract
MicroRNA-31 (miR-31) is among the most frequently altered microRNAs in human cancers and altered expression of miR-31 has been detected in a large variety of tumor types, but the functional role of miR-31 still hold both tumor suppressive and oncogenic roles in different tumor types. MiR-31 expression was down-regulated in a large cohort of hepatocellular carcinoma (HCC) patients, and low expression of miR-31 was significantly associated with poor prognosis of HCC patients. Ectopic expression of miR-31 mimics suppressed HCC cell growth by transcriptional deregulation of cell cycle proteins. Additional study evidenced miR-31 directly to suppress HDAC2 and CDK2 expression by inhibiting mRNA translation in HCC cells. We also found that ectopic expression of miR-31 mimics reduced metastatic potential of HCC cells by selectively regulating epithelial-mesenchymal transition (EMT) regulatory proteins such as N-cadherin, E-cadherin, vimentin and fibronectin. HCC tissues derived from chemical-induced rat liver cancer models validated that miR-31 expression is significantly down-regulated, and that those cell cycle- and EMT-regulatory proteins are deregulated in rat liver cancer. Overall, we suggest that miR-31 functions as a tumor suppressor by selectively regulating cell cycle and EMT regulatory proteins in human hepatocarcinogenesis providing a novel target for the molecular treatment of liver malignancies.
Highlights
Hepatocellular carcinoma (HCC) is one of the most deadly cancers worldwide and has no effective treatment [1]
MiR-31 is aberrantly down-regulated in HCC and its expression is associated with the poor prognosis of patients with HCC
To validate the expression of miR-31 in liver cancer, we observed miR-31 expression in the large cohorts of HCC patients available from the National Center for Biotechnology Information (NCBI) and Gene Expression Omnibus (GEO) database, and the data were presented as scatter plots
Summary
Hepatocellular carcinoma (HCC) is one of the most deadly cancers worldwide and has no effective treatment [1]. Even though the overall survival rate of liver cancer patients was increased thanks to recent studies, there are still no systemic treatment showing consistently efficient for liver cancer [2]. Aberrant regulation of non-coding RNAs (ncRNAs) has been proposed to be associated with hepatocarcinogenesis. The ncRNAs www.impactjournals.com/oncotarget can be divided into two major categories, long noncoding RNAs and short non-coding RNAs [4]. The most extensively studied small RNAs in cancer are microRNAs (miRNAs). Elegant studies over the past 15 years have defined an intricate mechanistic basis for miRNA-mediated silencing of target gene expression through the RNA-induced silencing complex, which employs Argonaute family proteins to cleave target mRNA transcripts or inhibit the translation of that mRNA [4]
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