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Wanted DEAD/H or Alive: Helicases Winding Up in Cancers. (J Natl Cancer Inst., Jan 2017)

Cai W1, Xiong Chen Z1, Rane G1, Satendra Singh S1, Choo Z1, Wang C1, Yuan Y1, Zea Tan T1, Arfuso F1, Yap CT1, Pongor LS1, Yang H1, Lee MB1, Cher Goh B1, Sethi G1, Benoukraf T1, Tergaonkar V1, Prem Kumar A2.

Cancer Science Institute of Singapore, National University of Singapore, Singapore (WC, GR, SSS, CW, YY, TZT, HY, BCG, TB, APK);
Departments of Pharmacology (WC, GR, SSS, CW, BCG, GS, APK), Physiology (ZXC, ZC, CTY), and Biochemistry (VT), Yong Loo Lin School of Medicine, National University of Singapore, Singapore;
KK Women’s and Children’s Hospital, Singapore (ZXC);
Stem Cell and Cancer Biology Laboratory (FA), School of Biomedical Sciences (GS, APK), Curtin Health Innovation Research Institute, Curtin Medical School (APK), Curtin University, Perth, WA, Australia;
National University Cancer Institute, National University Health System, Singapore (CTY, BCG, APK);
Department of Pediatrics, Semmelweis University, Budapest, Hungary (LSP);
MTA TTK Lendület Cancer Biomarker Research Group, Research Centre for Natural Sciences, Budapest, Hungary (LSP);
Department of Renal Medicine (MBL) and Department of Haematology-Oncology (BCG), National University Health System, Singapore;
Institute of Molecular and Cell Biology (IMCB), A∗STAR (Agency for Science, Technology and Research), Singapore (VT);
Centre for Cancer Biology, University of South Australia and SA Pathology, Adelaide, Australia (VT);
Department of Biological Sciences, University of North Texas, Denton, TX (APK).

Abstract

Cancer is one of the most studied areas of human biology over the past century. Despite having attracted much attention, hype, and investments, the search to find a cure for cancer remains an uphill battle. Recent discoveries that challenged the central dogma of molecular biology not only further increase the complexity but also demonstrate how various types of noncoding RNAs such as microRNA and long noncoding RNA, as well as their related processes such as RNA editing, are important in regulating gene expression. Parallel to this aspect, an increasing number of reports have focused on a family of proteins known as DEAD/H-box helicases involved in RNA metabolism, regulation of long and short noncoding RNAs, and novel roles as “editing helicases” and their association with cancers. This review summarizes recent findings on the roles of RNA helicases in various cancers, which are broadly classified into adult solid tumors, childhood solid tumors, leukemia, and cancer stem cells. The potential small molecule inhibitors of helicases and their therapeutic value are also discussed. In addition, analyzing next-generation sequencing data obtained from public portals and reviewing existing literature, we provide new insights on the potential of DEAD/H-box helicases to act as pharmacological drug targets in cancers.

PMID: 28122908