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Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Jan 27, 2015; 7(1): 1-6
Published online Jan 27, 2015. doi: 10.4254/wjh.v7.i1.1
Diagnostic and therapeutic application of noncoding RNAs for hepatocellular carcinoma
Chikako Shibata, Motoyuki Otsuka, Takahiro Kishikawa, Motoko Ohno, Takeshi Yoshikawa, Akemi Takata, Kazuhiko Koike
Chikako Shibata, Motoyuki Otsuka, Takahiro Kishikawa, Motoko Ohno, Takeshi Yoshikawa, Akemi Takata, Kazuhiko Koike, Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan
Motoyuki Otsuka, Japan Science and Technology Agency, PRESTO, Kawaguchi, Saitama 332-0012, Japan
Author contributions: Shibata C, Otsuka M and Koike K designed and wrote the manuscript; Kishikawa T, Ohno M, Yoshikawa T and Takata A prepared the tables and references.
Supported by Grants-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology, Japan, Nos. #25293076, #26860492, #25860520, and #24390183 (to Otsuka M, Kishikawa T, Yoshikawa T and Koike K); by Health Sciences Research Grants of The Ministry of Health, Labour and Welfare of Japan (to Koike K); by grants from the Japanese Society of Gastroenterology, Okinaka Memorial Institute for Medical Research, and Honjo International Scholarship Foundation (to Otsuka M); by a grant from the Mishima Kaiun Memorial Foundation (to Ohno M)
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Motoyuki Otsuka, MD, Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 5-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
Telephone: +81-3-38155411 Fax: +81-3-38140021
Received: August 19, 2014
Peer-review started: August 20, 2014
First decision: September 16, 2014
Revised: September 21, 2014
Accepted: November 17, 2014
Article in press: November 19, 2014
Published online: January 27, 2015

MicroRNAs (miRNAs) are small, noncoding RNA molecules that regulate gene expression posttranscriptionally, targeting thousands of messenger RNAs. Long noncoding RNAs (lncRNAs), another class of noncoding RNAs, have been determined to be also involved in transcription regulation and translation of target genes. Since deregulated expression levels or functions of miRNAs and lncRNAs in hepatocellular carcinoma (HCC) are frequently observed, clinical use of noncoding RNAs for novel diagnostic and therapeutic applications in the management of HCCs is highly and emergently expected. Here, we summarize recent findings regarding deregulated miRNAs and lncRNAs for their potential clinical use as diagnostic and prognostic biomarkers of HCC. Specifically, we emphasize the deregulated expression levels of such noncoding RNAs in patients’ sera as noninvasive biomarkers, a field that requires urgent improvement in the clinical surveillance of HCC. Since nucleotide-based strategies are being applied to clinical therapeutics, we further summarize clinical and preclinical trials using oligonucleotides involving the use of miRNAs and small interfering RNAs against HCC as novel therapeutics. Finally, we discuss current open questions, which must be clarified in the near future for realistic clinical applications of these new strategies.

Keywords: MicroRNA, Long noncoding RNA, Hepatocellular carcinoma, Clinical trials, Biomarker

Core tip: In this review, we summarize the latest findings on deregulated microRNAs (miRNAs) and long noncoding RNAs in hepatocellular carcinomas (HCCs) with a focus on their clinical use as novel diagnostic and prognostic biomarkers. In addition, we summarize the current status of clinical and preclinical oligonucleotide therapies including miRNAs and small interfering RNAs as novel HCC therapeutics. This review will enable the readers to understand the current status of clinical applications and knowledge of noncoding RNAs in HCC management.