Chemo-resistance, which is the main obstacle in
cancer therapy, is caused by the onset of drug-resistant cells in the heterogeneous cell population in
cancer tissues.
MicroRNAs regulate gene expression at the post-transcriptional level, and they are involved in many different biological processes, including cell proliferation, differentiation, metabolism, stress response, and apoptosis. The aberrant expression of
microRNAs plays a major pathogenic role from the early stages of the
carcinogenesis process. Recently,
microRNAs have been reported to play an important role in inducing resistance to anti-
cancer drugs. Specific
microRNA alterations occur selectively in
cancer cells, rendering these cells resistant to various chemotherapeutic agents. For example, resistance to
5-fluorouracil is mediated by alterations in miR-21, miR-27a/b, and miR-155; the sensitivity to
Docetaxel is influenced by miR-98, miR-192, miR-194, miR-200b, miR-212, and miR-424; and the resistance to
Cisplatin is mediated by miR-let-7, miR-15, miR-16 miR-21 and miR-214. Chemo-resistant
cancer cells are characterized by altered functions in
enzymes that are involved in
microRNA maturation, primarily including Dicer, as demonstrated in
ovarian cancer,
oral squamous cell carcinoma,
breast cancer and
cervical cancer. Based on the evidence reviewed in this paper, various strategies have been developed to artificially re-establish
microRNA expression in resistant cells, thus restoring chemo-sensitivity. These strategies employ synthetic analogs, anti-
microRNA oligonucleotides,
locked nucleic acid,
microRNA sponges, drugs that inhibit DNA methylation or
histone deacetylation, and the introduction of
microRNA mimics. The ability to modulate
microRNA expression is a promising strategy for overcoming the problem of drug resistance in
cancer treatment.