Competing endogenous RNA networks in ovarian cancer: from bench to bedside

Abstract

Epithelial ovarian cancer is responsible for the majority of ovarian malignancies, and its highly invasive nature and chemoresistant development have been major obstacles to treating patients with mainstream treatments. In recent decades, the significance of microRNAs (miRNAs), circular RNAs (circRNAs), long non-coding RNAs (lncRNAs), and competing endogenous RNAs (ceRNAs) has been highlighted in ovarian cancer development. This hidden language between these RNAs has led to the discovery of enormous regulatory networks in ovarian cancer cells that substantially affect gene expression. Aside from providing ample opportunities for targeted therapies, circRNA- and lncRNA-mediated ceRNA network components provide invaluable biomarkers. The current study provides a comprehensive and up-to-date review of the recent findings on the significance of these ceRNA networks in the hallmarks of ovarian cancer oncogenesis, treatment, diagnosis, and prognosis. Also, it provides the authorship with future perspectives in the era of single-cell RNA sequencing and personalized medicine.

Keywords: circular RNA; competing endogenous RNAs; long non-coding RNA; microRNAs; ovarian cancer.

Table 1. ceRNA networks in the proliferation and cell cycle of ovarian cancer

Table 2. ceRNA networks in the apoptosis, ferroptosis, and pyroptosis of ovarian cancer

Table 3. ceRNA networks in the migration and invasion of ovarian cancer

Table 4. ceRNA networks in the stemness of ovarian cancer

Figure 1. The cell cycle and apoptosis pathways A) The cell cycle consists of G₁, S, G₂, and M phases that are regulated by proto-oncogenes and tumor-suppressive genes. B) Intrinsic and extrinsic apoptosis pathways are two distinct pathways that mediate apoptosis by converging into caspase 3 and caspase 7.

Figure 2. The epithelial-to-mesenchymal transition and angiogenesis in cancer. A) In the epithelial-to-mesenchymal transition, the malignant cells acquire a mesenchymal phenotype, allowing them to become more invasive. B) The tumor-released growth factors, like VEGFs, facilitate angiogenesis, which is a hallmark of malignancy.

Figure 3. Cancer glycolysis pathway and cancer stem cell model. A) The pathway of glycolytic processes in cancer cells. B) Cancer stem cell model that demonstrates a small population of malignant cells can become resistant to anti-neoplastic treatments and can reproduce tumor bulk after treatment.

Figure 4. Tumor-suppressive tumor microenvironment and competing endogenous RNA in ovarian cancer. The FGD5-AS1/miR-142-5p/PD-L1 axis can promote the inhibitory immune checkpoint axis of PD-1 and PD-L1, leading to tumor growth.

Figure 5. Liquid biopsy for ovarian cancer. Tumor-released factors, including circulating tumor cells, tumor-educated platelets, circulating tumor DNA, and exosomes, can be leveraged as biomarkers for ovarian cancer.