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Review
. 2021 Feb 8;14(2):136.
doi: 10.3390/ph14020136.

MicroRNA-Based Therapeutics for Drug-Resistant Colorectal Cancer

Eunsun Jung  1 , Jinhyeon Choi  1 , Jang-Seong Kim  1 , Tae-Su Han  1
Affiliations
Review

MicroRNA-Based Therapeutics for Drug-Resistant Colorectal Cancer

Eunsun Jung et al. Pharmaceuticals (Basel). .

Abstract

Although therapeutic approaches for patients with colorectal cancer (CRC) have improved in the past decades, the problem of drug resistance still persists and acts as a major obstacle for effective therapy. Many studies have shown that drug resistance is related to reduced drug uptake, modification of drug targets, and/or transformation of cell cycle checkpoints. A growing body of evidence indicates that several microRNAs (miRNAs) may contribute to the drug resistance to chemotherapy, targeted therapy, and immunotherapy by regulating the drug resistance-related target genes in CRC. These drug resistance-related miRNAs may be used as promising biomarkers for predicting drug response or as potential therapeutic targets for treating patients with CRC. In this review, we summarized the recent discoveries regarding anti-cancer drug-related miRNAs and their molecular mechanisms in CRC. Furthermore, we discussed the challenges associated with the clinical application of miRNAs as biomarkers for the diagnosis of drug-resistant patients and as therapeutic targets for CRC treatment.

Keywords: anti-cancer drug resistance; chemoresistance; colorectal cancer; immunotherapy; microRNA; targeted therapy.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The canonical pathway of microRNA (miRNA) processing. In the nucleus, miRNA biogenesis is initiated with RNA polymerase II. Pri-miRNA with a hairpin transcript is further processed to pre-miRNA by the DGCR8/Drosha microprocessor complex. The pre-miRNA is then translocated to the cytoplasm through exportin-5. In the cytoplasm, multidomain human TAR element-binding protein (TRBP) recognizes pre-miRNA and is cleaved by Dicer, resulting in miRNA maturation. In the miRNA-duplex, only one strand is loaded onto the RNA-induced silencing complex (RISC) complex (including the AGO1-4 protein), which then binds to the complementary target gene. Finally, the target mRNA can be suppressed through translation repression or degradation.
Figure 2
Figure 2
Summary for drug resistance-related miRNAs in CRC.
See this image and copyright information in PMC

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