Title:Mechanism of Cancer Drug Resistance and the Involvement of Noncoding RNAs
VOLUME: 21 ISSUE: 26
Author(s):Hongping Xia and Kam M. Hui
Affiliation:Division of Cellular and Molecular Research, National Cancer Centre Singapore, 11 Hospital Drive, Singapore 169610.
Keywords:Cancer stem cells, Drug resistance, Epithelial-mesenchymal transition (EMT), Long non-coding RNAs (lncRNAs),
MicroRNA.
Abstract:Drug resistance is one of the major reasons for the failure of cancer therapies. Although our understanding of
resistance to targeted cancer drugs remains incomplete, new and more creative approaches are being exploited to intercept
this phenomenon. Considerable advances have been made in our understanding that cancer drug resistance can be caused
by alterations of drug efflux, increases in drug metabolism, mutations of drug targets, alterations in DNA repair and cell
cycle, changes in cell apoptosis and autophagy, induction of epithelial-mesenchymal transition (EMT) and the generation
of cancer stem cells (CSCs). Furthermore, intracellular signalling pathways have been shown to play key physiological
roles and the abnormal activation of signalling pathways may be correlated with drug resistance. Recently, noncoding
RNAs (ncRNAs), including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), have emerged as important
regulators of gene expression and alternative splicing, which provides cells with yet another mode to greatly increase
regulatory complexity and fine-tune their transcriptome and can rapidly adjust their proteome in response to stimuli. Consequently,
a wide variety of biological functions have been shown to depend on the coordinated interactions between noncoding
RNAs and cellular signalling networks to achieve a concerted desired physiological outcome, whereas mutations
and dysregulation of ncRNAs have been linked to diverse human diseases, including cancer drug resistance. In this review,
we will discuss recent findings on the multiple molecular roles of regulatory ncRNAs on the signalling pathways
involved in cancer drug resistance and the therapeutic potential of reverse drug resistance.