Abstract
Hepatocellular carcinoma (HCC) is common and one of the most aggressive of all human cancers. Recent studies have indicated that miRNAs, a class of small noncoding RNAs that regulate gene expression post-transcriptionally, directly contribute to HCC by targeting many critical regulatory genes. Several miRNAs are involved in hepatitis B or hepatitis C virus replication and virus-induced changes, whereas others participate in multiple intracellular signaling pathways that modulate apoptosis, cell cycle checkpoints, and growth-factor-stimulated responses. When disturbed, these pathways appear to result in malignant transformation and ultimately HCC development. Recently, miRNAs circulating in the blood have acted as possible early diagnostic markers for HCC. These miRNA also could serve as indicators with respect to drug efficacy and be prognostic in HCC patients. Such biomarkers would assist stratification of HCC patients and help direct personalized therapy. Here, we summarize recent advances regarding the role of miRNAs in HCC development and progression. Our expectation is that these and ongoing studies will contribute to the understanding of the multiple roles of these small noncoding RNAs in liver tumorigenesis.
Highlights
Hepatocellular carcinoma (HCC) is common and one of the most aggressive of all human cancers
Recent studies have indicated that miRNAs, a class of small noncoding RNAs that regulate gene expression post-transcriptionally, directly contribute to HCC by targeting many critical regulatory genes
Chronic hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infections resulting in hepatic fibrosis and cirrhosis are the major risk factors for HCC, and we are currently seeing the long-term consequence of extensive HCV transmission in the aging baby boomer populations in the United States
Summary
ZHAO Xue1†, YANG Zhen2†, LI GuangBing, LI DongKai, ZHAO Yi4, WU Yan, ROBSON Simon C.5, HE Lian, XU YiYao1*, MIAO RuoYu1,4* & ZHAO HaiTao1*. Therapeutic intervention with hypomethylating agents could inhibit HCC cell growth by increasing miR-1-1 expression to inhibit expression of its two downstream oncogenes, MET (MNNG HOS transforming gene) and FoxP1 (Forkhead box protein P1) [80] These data imply that compounds interfering with epigenetic modifications, such as DNMT and histone deacetylase inhibitors, may serve as potential novel antitumor drugs for HCC patients [81,82]. These data are indicative of a negative modulation of Bcl-xL expression at mRNA and protein levels by let-7 miRNA [87] Downregulation of these miRNAs in HCC cells enables them to evade apoptosis and survive in nutrient-depleted and hypoxic microenvironments. Serum levels of let-7a, let-7f and miR-98 were significantly increased even at very early stages of hepatocarcinogenesis These miRNAs may help to evaluate and stratify HCC patients for an optimal personalized therapy
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