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Review
. 2015 Aug 18;4(8):1631-50.
doi: 10.3390/jcm4081631.

MicroRNAs: Emerging Novel Clinical Biomarkers for Hepatocellular Carcinomas

Sumadi Lukman Anwar  1   2 , Ulrich Lehmann  3
Affiliations
Review

MicroRNAs: Emerging Novel Clinical Biomarkers for Hepatocellular Carcinomas

Sumadi Lukman Anwar et al. J Clin Med. .

Abstract

The discovery of small non-coding RNAs known as microRNAs has refined our view of the complexity of gene expression regulation. In hepatocellular carcinoma (HCC), the fifth most frequent cancer and the third leading cause of cancer death worldwide, dysregulation of microRNAs has been implicated in all aspects of hepatocarcinogenesis. In addition, alterations of microRNA expression have also been reported in non-cancerous liver diseases including chronic hepatitis and liver cirrhosis. MicroRNAs have been proposed as clinically useful diagnostic biomarkers to differentiate HCC from different liver pathologies and healthy controls. Unique patterns of microRNA expression have also been implicated as biomarkers for prognosis as well as to predict and monitor therapeutic responses in HCC. Since dysregulation has been detected in various specimens including primary liver cancer tissues, serum, plasma, and urine, microRNAs represent novel non-invasive markers for HCC screening and predicting therapeutic responses. However, despite a significant number of studies, a consensus on which microRNA panels, sample types, and methodologies for microRNA expression analysis have to be used has not yet been established. This review focuses on potential values, benefits, and limitations of microRNAs as new clinical markers for diagnosis, prognosis, prediction, and therapeutic monitoring in HCC.

Keywords: biomarker; diagnosis; hepatocellular carcinoma; microRNA; prognosis; therapeutic monitoring.

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Figures

Figure 1
Figure 1
Biogenesis of microRNA (A) and transcriptional inhibition by microRNA (B). MicroRNA is transcribed from microRNA genes by RNA polymerase II into primordial-microRNAs. Segments of pri-miRNA contain a stem-loop structure that can be recognized by DiGeorge Syndrome Critical Region gene 8 (DGCR8) proteins for subsequent processing by RNase type III Drosha to produce pre-microRNAs. The hairpin-contained pre-microRNAs are then exported from the nucleus to the cytoplasm by a protein complex containing exportin-5 and RNA-GTP. In the cytoplasm, pre-microRNAs are further sliced by RNase type III Dicer, eliciting double-strand, ~22 nucleotide-long, mature microRNAs. After the duplex mature microRNA unwinds, degradation of the other strand follows. The single stranded mature microRNA within the RISC complex can subsequently act as a binding site to the messenger RNA (mRNA) targets. Perfect or nearly perfect complementarity to the 3′ UTR of mRNA results in cleavage of the mRNA targets. Partial complementarity of miRNA results in translational inhibition.
Figure 1
Figure 1
Biogenesis of microRNA (A) and transcriptional inhibition by microRNA (B). MicroRNA is transcribed from microRNA genes by RNA polymerase II into primordial-microRNAs. Segments of pri-miRNA contain a stem-loop structure that can be recognized by DiGeorge Syndrome Critical Region gene 8 (DGCR8) proteins for subsequent processing by RNase type III Drosha to produce pre-microRNAs. The hairpin-contained pre-microRNAs are then exported from the nucleus to the cytoplasm by a protein complex containing exportin-5 and RNA-GTP. In the cytoplasm, pre-microRNAs are further sliced by RNase type III Dicer, eliciting double-strand, ~22 nucleotide-long, mature microRNAs. After the duplex mature microRNA unwinds, degradation of the other strand follows. The single stranded mature microRNA within the RISC complex can subsequently act as a binding site to the messenger RNA (mRNA) targets. Perfect or nearly perfect complementarity to the 3′ UTR of mRNA results in cleavage of the mRNA targets. Partial complementarity of miRNA results in translational inhibition.
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