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Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 21, 2018; 24(27): 2949-2973
Published online Jul 21, 2018. doi: 10.3748/wjg.v24.i27.2949
MicroRNAs in the prognosis and therapy of colorectal cancer: From bench to bedside
Kenneth KW To, Christy WS Tong, Mingxia Wu, William CS Cho
Kenneth KW To, Christy WS Tong, Mingxia Wu, School of Pharmacy, Faculty of Medicine, the Chinese University of Hong Kong, Hong Kong, China
William CS Cho, Department of Clinical Oncology, Queen Elizabeth Hospital, Hong Kong, China
Author contributions: All authors contributed equally to this paper with conception and design of the study, literature review and analysis, drafting and critical revision and editing, and final approval of the submitted version.
Supported by the Direct Grant for Research, Faculty of Medicine, the Chinese University of Hong Kong, No. 4054371.
Conflict-of-interest statement: No potential conflicts of interest. No financial support.
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: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Kenneth KW To, PhD, Associate Professor, School of Pharmacy, Faculty of Medicine, the Chinese University of Hong Kong, Room 801N, Lo Kwee Seong Integrated Biomedical Sciences Building, Area 39, Shatin, New Territories, Hong Kong, China. kennethto@cuhk.edu.hk
Telephone: +852-39438017 Fax: +852-26035295
Received: May 2, 2018
Peer-review started: May 4, 2018
First decision: June 6, 2018
Revised: June 28, 2018
Accepted: June 30, 2018
Article in press: June 30, 2018
Published online: July 21, 2018
Abstract

MicroRNAs (miRNAs) are small, single-stranded, noncoding RNAs that can post-transcriptionally regulate the expression of various oncogenes and tumor suppressor genes. Dysregulated expression of many miRNAs have been shown to mediate the signaling pathways critical in the multistep carcinogenesis of colorectal cancer (CRC). MiRNAs are stable and protected from RNase-mediated degradation, thereby enabling its detection in biological fluids and archival tissues for biomarker studies. This review focuses on the role and application of miRNAs in the prognosis and therapy of CRC. While stage II CRC is potentially curable by surgical resection, a significant percentage of stage II CRC patients do develop recurrence. MiRNA biomarkers may be used to stratify such high-risk population for adjuvant chemotherapy to provide better prognoses. Growing evidence also suggests that miRNAs are involved in the metastatic process of CRC. Certain of these miRNAs may thus be used as prognostic biomarkers to identify patients more likely to have micro-metastasis, who could be monitored more closely after surgery and/or given more aggressive adjuvant chemotherapy. Intrinsic and acquired resistance to chemotherapy severely hinders successful chemotherapy in CRC treatment. Predictive miRNA biomarkers for response to chemotherapy may identify patients who will benefit the most from a particular regimen and also spare the patients from unnecessary side effects. Selection of patients to receive the new targeted therapy is becoming possible with the use of predictive miRNA biomarkers. Lastly, forced expression of tumor suppressor miRNA or silencing of oncogenic miRNA in tumors by gene therapy can also be adopted to treat CRC alone or in combination with other chemotherapeutic drugs.

Keywords: MicroRNA, Colorectal cancer, Multidrug resistance, Prognosis, Therapeutic target, Apoptosis, Metastasis, Recurrence, Risk stratification

Core tip: MicroRNAs (miRNAs) are important mediators regulating the initiation, progression, metastasis and recurrence of colorectal cancer (CRC). Numerous studies have reported dysregulation of miRNAs in tumor specimens and body fluids, including serum, plasma and feces. Furthermore, the miRNAs were more recently found in circulating exosomes from CRC patients. Fortunately, this finding suggests potential diagnostic, prognostic and therapeutic applications of miRNAs at different stages of CRC. In this review, we aim to outline the current body of knowledge pertaining to the critical roles played by miRNAs in the molecular pathogenesis of CRC. Our focus is to delineate practical applications of miRNAs as prognostic biomarkers and therapeutic targets in the treatment of CRC.