Circular RNAs in gynecologic cancers: mechanisms and implications for chemotherapy resistance

Abstract

Chemotherapy resistance remains a major challenge in the treatment of gynecologic malignancies. Increasing evidence suggests that circular RNAs (circRNAs) play a significant role in conferring chemoresistance in these cancers. In this review, we summarize the current understanding of the mechanisms by which circRNAs regulate chemotherapy sensitivity and resistance in gynecologic malignancies. We also discuss the potential clinical implications of these findings and highlight areas for future research. CircRNAs are a novel class of RNA molecules that are characterized by their unique circular structure, which confers increased stability and resistance to degradation by exonucleases. Recent studies have shown that circRNAs can act as miRNA sponges, sequestering miRNAs and preventing them from binding to their target mRNAs. This can lead to upregulation of genes involved in drug resistance pathways, ultimately resulting in decreased sensitivity to chemotherapy. We discuss several specific examples of circRNAs that have been implicated in chemoresistance in gynecologic cancers, including cervical cancer, ovarian cancer, and endometrial cancer. We also highlight the potential clinical applications of circRNA-based biomarkers for predicting chemotherapy response and guiding treatment decisions. Overall, this review provides a comprehensive overview of the current state of knowledge regarding the role of circRNAs in chemotherapy resistance in gynecologic malignancies. By elucidating the underlying mechanisms by which circRNAs regulate drug sensitivity, this work has important implications for improving patient outcomes and developing more effective therapeutic strategies for these challenging cancers.

Drug resistance in ovarian cancer: from mechanism to clinical trial

“…NcRNAs, comprising long ncRNAs (lncRNAs), small ncRNAs (sncRNAs) and circular RNAs (circRNAs), can regulate gene expression via epigenetic modification [ 173 ]. Most commonly, lncRNAs and circRNAs play roles in drug resistance by acting as miRNA sponges to regulate downstream gene expression [ 174 ]. “Epi-miRNAs” exert their effects by directly targeting epigenetic regulators, such as DNMTs and HDACs, or components of polycomb repressor complexes [ 175 ].…”

The role of circRNAs in regulation of drug resistance in ovarian cancer

“…Furthermore, circRNAs have been identified to regulate drug resistance in ovarian cancer ( Lan et al, 2021 ). In addition, drug resistance changes the expression of certain circRNAs ( Qin et al, 2023a ). However, the role and molecular mechanism of circRNAs in ovarian cancer are elusive ( Liu et al, 2022c ).…”

“…It is pivotal to mention that there is an interaction between circRNAs and drug resistance in ovarian cancer. Some circRNAs regulate drug resistance in ovarian cancer, while drug resistance changes the expression of certain circRNAs ( Qin et al, 2023a ). Moreover, circRNAs could be potential biomarkers for prediction of drug resistance in ovarian cancer.…”

The emerging roles of long non-coding RNA (lncRNA) H19 in gynecologic cancers

“…The treatment of GCs depends on various factors including the type and stage of cancer [ 18 ], overall health of the patient, and the patient’s preferences [ 19 ]. Treatment options may include surgery to remove the cancerous tissue (laparoscopy, hysterectomy, oophorectomy) [ 20 ], radiation therapy using high-energy radiation beams to destroy cancer cells (externally or internally) [ 21 ], chemotherapy to kill cancer cells (orally or intravenously) in combination with surgery or radiation therapy [ 22 ], targeted drugs [ 23 ], and immunotherapy [ 24 ]. Over the years, treatment strategies for GCs have become more personalized and targeted [ 25 ].…”