Long non‐coding RNA FEZF1‐AS1 induced progression of ovarian cancer via regulating miR‐130a‐5p/SOX4 axis

Abstract

Emerging studies have revealed the critical role of long non‐coding RNAs (lncRNAs) in epithelial ovarian cancer (EOC) development and progression. Till now, the roles and potential mechanisms regarding FEZF1 antisense RNA 1 (FEZF1‐AS1) within ovarian cancer (OC) remain unclear. The objective of this study was to uncover the biological function and the underlying mechanism of LncRNA FEZF1‐AS1 in OC progression. FEZF1‐AS1 expression levels were studied in cell lines and tissues of human ovarian cancer. In vitro studies were performed to evaluate the impact of FEZF1‐AS1 knock‐down on the proliferation, invasion, migration and apoptosis of OC cells. Interactions of FEZF1‐AS1 and its target genes were identified by luciferase reporter assays. Our data showed overexpression of FEZF1‐AS1 in OC cell lines and tissues. Cell migration, proliferation, invasion, wound healing and colony formation were suppressed by silencing of FEZF1‐AS1. In contrast, cell apoptosis was promoted by FEZF1‐AS1 knock‐down in vitro. Furthermore, online bioinformatics analysis and tools suggested that FEZF1‐AS1 directly bound to miR‐130a‐5p and suppressed its expression. Moreover, the inhibitory effects of miR‐130a‐5p on the OC cell growth were reversed by FEZF1‐AS1 overexpression, which was associated with the increase in SOX4 expression. In conclusion, our results revealed that FEZF1‐AS1 promoted the metastasis and proliferation of OC cells by targeting miR‐130a‐5p and its downstream SOX4 expression.

The Challenges and Opportunities of LncRNAs in Ovarian Cancer Research and Clinical Use

“…Closely related to this, and affected by fewer lncRNAs, is anchorage-independent cell proliferation, which measures the ability of cells to survive and proliferate in the absence of a solid support, a characteristic of malignant cells. After mouse xenografting, lncRNAs have also been shown to influence the size and weight of the tumor, some replicating the same scenario as in patients, such as AB073614 [9], EPB41L4A-AS2 [23], GAS5 [22], KCNQ1OT1 [35], LINC00565 [37], TINCR [51] and TPT1-AS1 [53].…”

The Emerging Role of Non-coding RNAs in Drug Resistance of Ovarian Cancer

“…At present, it is known that lncRNAs can regulate the malignant biological behavior of cells by acting as a competitive endogenous RNA (ceRNA), recruiting downstream molecules, serving as protein scaffolds, transmitting regulatory signals (Wong et al, 2018), and regulating endolysosome pH (Miller et al, 2018). A number of lncRNAs have a close relationship to the development of ovarian cancer metastasis, recurrence, and chemotherapy resistance (Winham et al, 2019;Zhang M. et al, 2019;Sun et al, 2020). Aberrantly expressed lncRNAs may participate in ovarian cancer progression through various mechanisms, including inducing autophagy, increasing DNA damage repair, changing cell cycle progression and checkpoints, inducing anti-apoptosis, regulating cell signaling pathways, and promoting EMT (Liu et al, 2015;Yan et al, 2017;Xu Q. F. et al, 2018;Wu et al, 2019).…”

Mechanisms of Apoptosis-Related Long Non-coding RNAs in Ovarian Cancer

“…High levels of FEZF1-AS1 are detected in tumor tissues and the serum of EOC patients, with its high expression associated with shorter overall survival of EOC patients ( Sun et al, 2020 ). Moreover, its knockdown promotes apoptosis in COC1 and SKOV3 ovarian cancer cells, suggesting the apoptosis-suppressive role of FEZF1-AS1 .…”

“…In vitro analyses of FEZF1-AS1 have shown that it functions as a competing endogenous RNA (ceRNA) for miR-130a-5p , or sponges miR-130a-5p ( Figure 1C ). Consequently, FEZF1-AS1 upregulates the expression of a miR-130a-5p target gene, sex-determining region Y (SRY)-box transcription factor 4 (SOX4) , that promotes proliferation of COC1 and SKOV3 cells and may contribute to apoptosis suppression ( Sun et al, 2020 ). Further analysis of FEZF1-AS1 function, especially in vivo , will clarify its role and significance in apoptosis of ovarian cancer cells.…”