Circular RNAs in Epithelial Ovarian Cancer: From Biomarkers to Therapeutic Targets

Abstract

Epithelial ovarian cancer (EOC) is the most lethal gynecological cancer, and more than 70% of patients are diagnosed at advanced stages. Despite the application of surgery and chemotherapy, the prognosis remains poor due to the high relapse rate. It is urgent to identify novel biomarkers and develop novel therapeutic strategies for EOC. Circular RNAs (circRNAs) are a class of noncoding RNAs generated from the “back-splicing” of precursor mRNA. CircRNAs exert their functions via several mechanisms, including acting as miRNA sponges, interacting with proteins, regulating transcription, and encoding functional proteins. Recent studies have identified many circRNAs that are dysregulated in EOC and may be used as diagnostic and prognostic markers. Increasing evidence has revealed that circRNAs play a critical role in ovarian cancer progression by regulating various cellular processes, including proliferation, apoptosis, metastasis, and chemosensitivity. The circRNA-based therapy may be a novel strategy that is worth exploring in the future. Here, we provide an overview of EOC and circRNA biogenesis and functions. We then discuss the dysregulations of circRNAs in EOC and the possibility of using them as diagnostic/prognostic markers. We also summarize the role of circRNAs in regulating ovarian cancer development and speculate their potential as therapeutic targets.

The Crosstalk and Clinical Implications of CircRNAs and Glucose Metabolism in Gastrointestinal Cancers

“…Thus, circRNAs are characteristically stable and have longer half-lives than their precursor mRNAs and other noncoding RNAs (microRNAs and long noncoding RNAs). Some glycolysis-associated circRNAs, which are abnormally expressed in the plasma exosomes of patients with GI cancers, have the potential to be used as liquid biopsy biomarkers for early detection of GI cancers [ 100 ]. For example, circPDK1 is significantly upregulated in the plasma exosomes and tumor tissues of patients with PC and promotes cell proliferation and glycolysis in vitro and in vivo.…”

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

“…Evidence has suggested that circRNAs could play an oncogenic role or exert tumor suppressive functions in ovarian cancer ( Zhang et al, 2022a ; Ghafouri-Fard et al, 2022 ; Najafi, 2023 ). Moreover, circRNAs might be biomarkers for diagnosis and prognosis in ovarian cancer ( Qiu et al, 2022 ). For instance, circRNA1656 was reported to act as a potential biomarker in high grade serous ovarian cancer ( Gao et al, 2019a ).…”

CircRNA LDLR promotes proliferation and aerobic glycolysis of gastric cancer cells by targeting CHD1 with miR-449b-5p

“…miR-449b-5p is recognized as a tumor suppressor that regulates tumor proliferation, metastasis, and invasion ( Garber, 2004 ; Chen et al, 2020 ; Huang et al, 2020 ). CHD1, a regulator in maintaining genome stability, promotes DNA transcription by keeping DNA in an open and transcriptionally active state through ATP-dependent assembly, transfer, and removal of nucleosomes from DNA ( Li et al, 2020 ; Qiu et al, 2022 ). It has been emphasized that CHD1 degradation suppresses glioma cell proliferation and glycolysis ( Jeck et al, 2013 ).…”