Abstract
MicroRNAs (miRNAs) are small non-coding RNAs with a length of about 19–25 nt, which can regulate various target genes and are thus involved in the regulation of a variety of biological and pathological processes, including the formation and development of cancer. Drug resistance in cancer chemotherapy is one of the main obstacles to curing this malignant disease. Statistical data indicate that over 90% of the mortality of patients with cancer is related to drug resistance. Drug resistance of cancer chemotherapy can be caused by many mechanisms, such as decreased antitumor drug uptake, modified drug targets, altered cell cycle checkpoints, or increased DNA damage repair, among others. In recent years, many studies have shown that miRNAs are involved in the drug resistance of tumor cells by targeting drug-resistance-related genes or influencing genes related to cell proliferation, cell cycle, and apoptosis. A single miRNA often targets a number of genes, and its regulatory effect is tissue-specific. In this review, we emphasize the miRNAs that are involved in the regulation of drug resistance among different cancers and probe the mechanisms of the deregulated expression of miRNAs. The molecular targets of miRNAs and their underlying signaling pathways are also explored comprehensively. A holistic understanding of the functions of miRNAs in drug resistance will help us develop better strategies to regulate them efficiently and will finally pave the way toward better translation of miRNAs into clinics, developing them into a promising approach in cancer therapy.
Highlights
Cancer is a serious threat to human life and health, and in recent years, it has become a leading cause of death in humans
CcRCC patients with no PTENP1 expression have a lower survival rate. These results suggested that PTENP1 functions as a competitive endogenous RNA (ceRNA) in clear-cell renal cell carcinoma (ccRCC), which suppresses cancer progression
MiRNA-126 targets and inhibits Vascular endothelial growth factor A (VEGFA), improving the sensitivity of non-small cell lung cancer (NSCLC) to bevacizumab [175]. These results indicate that the combination of chemotherapy drugs and miRNAs in the treatment of cancer might have a great application value
Summary
Cancer is a serious threat to human life and health, and in recent years, it has become a leading cause of death in humans. Et al [96] found that miRNA-200c increases sensitivity to taxanes in vitro by targeting the TUBB3 gene, and it was downregulated in ovarian cancer cell lines and stage III ovarian tumors, and low levels of miRNA-200c correlates with poor prognosis. Ectopic expression of miRNA-214 reduces cell survival, induces apoptosis, and enhances sensitivity to CDDP through directly inhibiting BCL2-like 2 (Bcl2l2) expression in cervical cancer HeLa and C-33A cells.
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