Functions and mechanisms of circular RNAs in cancer radiotherapy and chemotherapy resistance

Abstract

Circular RNAs (circRNAs), one type of non-coding RNA, were initially misinterpreted as nonfunctional products of pre-mRNA mis-splicing. Currently, circRNAs have been proven to manipulate the functions of diverse molecules, including non-coding RNAs, mRNAs, DNAs and proteins, to regulate cell activities in physiology and pathology. Accumulating evidence indicates that circRNAs play critical roles in tumor genesis, development, and sensitivity to radiation and chemotherapy. Radiotherapy and chemotherapy are two primary types of intervention for most cancers, but their therapeutic efficacies are usually retarded by intrinsic and acquired resistance. Thus, it is urgent to develop new strategies to improve therapeutic responses. To achieve this, clarification of the underlying mechanisms affecting therapeutic responses in cancer is needed. This review summarizes recent progress and mechanisms of circRNAs in cancer resistance to radiation and chemotherapy, and it discusses the limitations of available knowledge and potential future directions.

CircRNAs in anticancer drug resistance: recent advances and future potential

“…In addition, although most circRNAs mediate drug resistance by acting as sponges, other molecular mechanisms have also been reported, such as maintaining the stability of downstream miRNAs [166]. Common mechanisms underlying drug resistance include DNA repair, abnormal activation of signaling pathways, cancer stemness and the EMT [218]. A primary action of chemotherapy is to mediate DNA damage in cells, which in turn induces cancer cell death.…”

The Roles of ceRNAs-Mediated Autophagy in Cancer Chemoresistance and Metastasis

“…Chemoresistance is one of the main causes for therapeutic failure in cancers. Dysregulated autophagy [ 8 , 107 , 108 ], lncRNAs [ 33 , 109 , 110 , 111 ], and circRNAs [ 107 , 112 , 113 , 114 , 115 ] have been indicated to be associated with drug resistance in cancers. ceRNAs can play important roles in the regulation of autophagy-mediated chemoresistance in cancers.…”

The emerging landscape of circular RNAs in immunity: breakthroughs and challenges

“…Such characteristic induces the property of circRNAs, covering microRNA(miRNA) sponge, showing an interaction to RNA-binding proteins (RBPs), and encoding proteins that has been recently identified [2]. CircRNAs are found to impact considerable physiological and pathology processes, covering regulated cell death, metabolism, cancer, as well as drug resistance [3][4][5]. Besides, circRNAs can be up-regulated and stable in exosomes, which has increased opportunities for intercellular communication [6].…”