Abstract
Chemoresistance frequently occurs in cancer treatment, which results in chemotherapy failure and is one of the most leading causes of cancer-related death worldwide. Understanding the mechanism of chemoresistance and exploring strategies to overcome chemoresistance have become an urgent need. Autophagy is a highly conserved self-degraded process in cells. The dual roles of autophagy (pro-death or pro-survival) have been implicated in cancers and chemotherapy. MicroRNA (miRNA) is a class of small non-coding molecules that regulate autophagy at the post-transcriptional level in cancer cells. The association between miRNAs and autophagy in cancer chemoresistance has been emphasized. In this review, we focus on the dual roles of miRNA-mediated autophagy in facilitating or combating chemoresistance, aiming to shed lights on the potential role of miRNAs as targets to overcome chemoresistance.
Highlights
Cancers with local organ invasion and distant metastasis often require systemic chemotherapy
The first mouse model with deletion of autophagy gene was established to study the role of autophagy in tumorigenesis, and the results indicated that the deletion of BECN1 increased the rate of spontaneous tumor formation compared with BECN1 wild-type [53]
The process of autophagy is tightly regulated by ATGs, targeting ATGs represent a promising strategy for reversal of drug resistance
Summary
Cancers with local organ invasion and distant metastasis often require systemic chemotherapy. Immunotherapy and targeted therapy are commonly used in clinic after chemoresistance occurs [12]. Among these strategies, targeting autophagy to combat chemoresistance is gradually coming into sight. Autophagy protects cancer cells from chemotherapeutic drugs to mediate drug resistance by eliminating damaged organelles and recycling degradation products. Abnormal expression of miRNAs has been implicated in regulating cell proliferation, apoptosis, metastasis, migration, autophagy, and drug resistance in a large number of cancer types [22]. In the field of oncotherapy, MRX34, a liposomal miR-34a mimic, is the most advanced miRNA drug, which was designed to deliver miR-34a mimic to cancer cells for the treatment of several solid tumors [27]. We discussed the correlation between miRNAs and autophagy in chemoresistance/chemosensitivity, illustrated the current interventions targeting miRNA/autophagy axis to combat chemoresistance, aiming to provide novel insights from the perspective of miRNA-mediated autophagy for promoting chemotherapeutic efficacy
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