CGE_2024v12n6

Cancer Genetics and Epigenetics 2024, Vol.12, No.6, 329-345 http://medscipublisher.com/index.php/cge 330 circRNAs, in the progression and metastasis of ovarian cancer. Additionally, we will explore their potential as biomarkers for early diagnosis, prognosis, and therapeutic targets. By summarizing the current understanding and recent advances in this field, this study hope to highlight the importance of ncRNAs in ovarian cancer and inspire further research into their clinical applications. 2 Overview and Types of Non-coding RNAs (ncRNAs) 2.1 MicroRNAs (miRNAs): regulation of gene expression and impact on ovarian cancer MicroRNAs (miRNAs) are small, approximately 22-nucleotide-long ncRNAs that regulate gene expression post-transcriptionally by binding to the 3' untranslated regions (3' UTRs) of target mRNAs, leading to their degradation or translational repression. miRNAs are involved in various cellular processes, including differentiation, proliferation, and apoptosis, and their dysregulation is a hallmark of many cancers, including ovarian cancer (Ratti et al., 2020). In ovarian cancer, miRNAs can function as either oncogenes or tumor suppressors. For instance, miRNA let-7b has been identified as a potent tumor suppressor that targets multiple oncogenes involved in cell growth and motility. However, its function can be inhibited by lncRNAs such as HOST2, which acts as a molecular sponge for let-7b, thereby promoting tumor cell migration, invasion, and proliferation (Gao et al., 2015). This interaction highlights the complex regulatory networks involving miRNAs and other ncRNAs in ovarian cancer. 2.2 Long Non-coding RNAs (lncRNAs): functional role in cancer progression Long non-coding RNAs (lncRNAs) are a class of ncRNAs longer than 200 nucleotides that play diverse roles in gene regulation at the transcriptional, post-transcriptional, and epigenetic levels. lncRNAs are known to be involved in various biological processes, including chromatin remodeling, transcriptional regulation, and RNA splicing. In the context of cancer, lncRNAs can act as oncogenes or tumor suppressors, influencing tumor growth, metastasis, and resistance to therapy (Forrest and Khalil, 2017; Zhang et al., 2020). In ovarian cancer, several lncRNAs have been identified as key regulators of tumor progression. For example, the lncRNA RHPN1-AS1 has been shown to promote epithelial ovarian cancer (EOC) cell proliferation and metastasis by acting as a competing endogenous RNA (ceRNA) against miR-596, thereby upregulating the expression of LETM1 and activating the FAK/PI3K/Akt signaling pathway (Rong et al., 2021). Another lncRNA, HOST2, has been reported to specifically bind to miRNA let-7b, inhibiting its tumor-suppressive functions and promoting ovarian cancer cell migration and invasion (Gao et al., 2015). Moreover, lncRNAs can modulate the epigenetic landscape of cancer cells. For instance, lncRNAs can coordinate chromatin dynamics, regulate DNA methylation, and modulate the stability of other ncRNAs and mRNAs, thereby contributing to the massive epigenomic alterations observed in many tumors (Neganova et al., 2020). The lncRNA EPIC1, for example, interacts with the oncogene MYC, promoting cell-cycle progression and enhancing tumor growth in various cancers (Wang et al., 2018; Li and Li, 2024). 2.3 Circular RNAs (circRNAs): Emerging Roles in Cancer Biology and Regulation of Gene Expression Circular RNAs (circRNAs) are a novel class of ncRNAs characterized by their covalently closed circular structure, which makes them more stable than linear RNAs. circRNAs are generated through a process called back-splicing, where a downstream splice donor site is joined to an upstream splice acceptor site. Due to their stability and abundance, circRNAs have emerged as important regulators of gene expression and potential biomarkers for various diseases, including cancer (Figure 1) (Tao et al., 2021).

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