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Review
. 2020 Mar 14;19(1):58.
doi: 10.1186/s12943-020-01180-y.

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

Chaochu Cui  1 , Jianbo Yang  2 , Xiao Li  1 , Dongling Liu  1 , Liwu Fu  3 , Xianwei Wang  4
Affiliations
Review

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

Chaochu Cui et al. Mol Cancer. .

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.

Keywords: Cancer therapy; Chemoresistance; Multidrug resistance; Radioresistance; Sensitivity; circRNAs.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Biogenesis, distribution and function of circRNAs. CircRNAs are generated from back splicing of pre-mRNAs in different manners (a, b, c and d). CircRNAs can regulate the activities and functions of DNAs, RNAs and proteins in host cells. In addition, they can be secreted into the extracellular space and transported into adjacent cells or body fluids to regulate cell activities. a. Base pairing-dependent circularization; b. RNA-binding protein (RBP)-dependent circularization; c. Lariat-driven circularization; d. GU-rich and C-rich element-dependent circularization
Fig. 2
Fig. 2
Responses of cancer cells to radiotherapy and chemotherapy. A completely sensitive response is ideal but rare, while radiotherapy and chemotherapy are usually impeded by acquired or intrinsic resistance. Acquired resistance can be loosely divided into cancer stem cell (CSC)-mediated and non-CSC-mediated resistance. CSC-mediated resistance is attributed to the potential ability of CSCs to proliferate and differentiate, which results in regressed tumor recurrence or seeds new tumors in a new place via metastasis. Non-CSC-mediated resistance factors include therapy stress-induced secondary mutations, tumor heterogeneity, altered endoplasmic reticulum (ER) stress, autophagy, drug distribution and metabolism, and so on. The intrinsic resistance mechanisms are similar to those mediating acquired resistance, but the difference is that the characteristics in intrinsic resistance are inherent and not induced by therapy stress
Fig. 3
Fig. 3
Roles of circRNAs in mechanisms mediating radioresistance and chemoresistance of cancers. In tumor microenvironment (TME), microorganisms modulate the critical chemical structures or local concentrations of drugs. In addition to regulating the distribution of drugs, noncancerous cells, such as CAFs and CAMs, can secrete soluble factors to promote therapy resistance. Remodeling of transporters or channels responsible for drug flux could result in decreased intracellular drug concentration. Amplification of targets or activation of aberrant downstream signals also impedes therapeutic efficacy by inducing ER stress, autophagy, mitophagy, stemness and DNA repair
See this image and copyright information in PMC

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