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CircRNA FGFR3 induces epithelial-mesenchymal transition of ovarian cancer by regulating miR-29a-3p/E2F1 axis.

ABSTRACT: Circular RNAs (circRNAs) are a class of non-coding RNAs that regulate gene expression after transcription. However, the specific function of circRNAs in ovarian cancer remains undetermined. Previous studies have demonstrated abnormal expression of circFGFR3 in several cancers. The present study was designed to reveal the roles of circFGFR3 in ovarian cancer (OC). CircFGFR3 expression in OC tissues and cells was detected by RT-qPCR. The effects of CircFGFR3 on OC cells were evaluated by transwell assay and CCK-8 assay. Finally, the underlying mechanism was further revealed by luciferase reporter assay and western blotting. Our results showed that circFGFR3 expression was higher in OC cells and tissues than in normal ovarian cells and adjacent normal tissues; in addition, in OC patients, a high level of CircFGFR3 was related to lower survival rates and higher recurrence rates than a low level of circFGFR3. CircFGFR3 overexpression promotes OC progression by inducing epithelial-mesenchymal transition (EMT) in vitro. Mechanistically, circFGFR3 upregulates E2F1 expression by sponging miR-29a-3p, and the overexpression of E2F1 or the suppression of miR-29a-3p induces OC cell EMT. Therefore, circFGFR3 serves as a promoter of OC by inducing OC cell EMT via the miR-29a-3p/E2F1 axis and circFGFR3 may be a prognostic biomarker for OC patients.

SUBMITTER: Zhou J

PROVIDER: S-EPMC7425466 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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CircRNA FGFR3 induces epithelial-mesenchymal transition of ovarian cancer by regulating miR-29a-3p/E2F1 axis.

Zhou Jing J Dong Ze-Ning ZN Qiu Bai-Quan BQ Hu Ming M Liang Xiao-Qing XQ Dai Xing X Hong Dan D Sun Yu-Fang YF

Aging 20200715 14

Circular RNAs (circRNAs) are a class of non-coding RNAs that regulate gene expression after transcription. However, the specific function of circRNAs in ovarian cancer remains undetermined. Previous studies have demonstrated abnormal expression of circFGFR3 in several cancers. The present study was designed to reveal the roles of circFGFR3 in ovarian cancer (OC). CircFGFR3 expression in OC tissues and cells was detected by RT-qPCR. The effects of CircFGFR3 on OC cells were evaluated by transwell ...[more]

PMID: 32668414

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Project description:BackgroundOvarian cancer is one of the most widespread malignant diseases of the female reproductive system worldwide. The plurality of ovarian cancer is diagnosed with metastasis in the abdominal cavity. Epithelial-mesenchymal transition (EMT) exerts a vital role in tumor cell metastasis. However, it remains unclear whether long non-coding RNA (lncRNA) are implicated in EMT and influence ovarian cancer cell invasion and metastasis. This study was designed to investigate the impacts of lncRNA AC005224.4 on ovarian cancer.MethodsLncRNA AC005224.4, miR-140-3p, and snail family transcriptional repressor 2 ( SNAI2 ) expression levels in ovarian cancer and normal ovarian tissues were determined using real-time quantitative polymerase chain reaction (qRT-PCR). Cell Counting Kit-8 (CCK-8) and Transwell (migration and invasion) assays were conducted to measure SKOV3 and CAOV-3 cell proliferation and metastasis. E-cadherin, N-cadherin, Snail, and Vimentin contents were detected using Western blot. Nude mouse xenograft assay was utilized to validate AC005224.4 effects in vivo . Dual-luciferase reporter gene assay confirmed the targeted relationship between miR-140-3p and AC005224.4 or SNAI2 .ResultsAC005224.4 and SNAI2 upregulation and miR-140-3p downregulation were observed in ovarian cancer tissues and cells. Silencing of AC005224.4 observably moderated SKOV3 and CAOV-3 cell proliferation, migration, invasion, and EMT process in vitro and impaired the tumorigenesis in vivo . miR-140-3p was a target of AC005224.4 and its reduced expression level was mediated by AC005224.4. miR-140-3p mimics decreased the proliferation, migration, and invasion of ovarian cancer cells. SNAI2 was identified as a novel target of miR-140-3p and its expression level was promoted by either AC005224.4 overexpression or miR-140-3p knockdown. Overexpression of SNAI2 also facilitated ovarian cancer cell viability and metastasis.ConclusionAC005224.4 was confirmed as an oncogene via sponging miR-140-3p and promoted SNAI2 expression, contributing to better understanding of ovarian cancer pathogenesis and shedding light on exploiting the novel lncRNA-directed therapy against ovarian cancer.

Project description:Purpose: Circular RNAs (circRNAs) have been reported to regulate the incidence of tumor by regulating the transcriptional level and post-transcriptional level of tumor-related genes, and are significantly correlated with tumor metastasis and progression. CircRNA_100395 (circ_100395) has been reported to suppress lung cancer cell proliferation, and might act as an oncogene in deveopment of various cancers. However, the expression and function of circ_100395 in ovarian cancer has not been systematically researched. Methods: The expression of circ_100395 in ovarian cancer tissues was detected by Real-time Quantitative polymerase chain reaction (RT-qPCR), while the relationship between circ_100395 expression and clinicopathological characteristics was further analyzed. After increasing the expression of circ_100395 by plasmid transfection in ovarian cancer cells, we further investigated the cell proliferation, invasion and migration by cell counting kit-8 (CCK-8), and Transwell assays. Epithelial-mesenchymal transition (EMT) pathway was also measured by western blotting. In addition, the relationship among circ_100395, miR-1228 and p53 in ovarian cancer, was explored by luciferase reporter assay. Results: The expression of circ_100395 was found to be significantly down-regulated in ovarian cancer, while low expression of circ_100395 was highly correlated with the poor outcomes. In addition, upregulation of circ_100395 could significantly inhibit tumor growth, metastasis and EMT signaling pathway in ovarian cancer. Furthermore, the expression level of circ_100395 was negatively correlated with the expression of miR-1228, and with the addition of miR-1228 could reverse anti-cell proliferation effect induced by circ_100395 in ovarian cancer cells. In addition, p53 might be the key target of circ_100395 / miR-1228 axis in ovarian cancer. Conclusion: CircRNA_100395 could inhibit cell growth and metastasis of ovarian cancer cells via regulating the miR-1228/p53/EMT axis.

Dataset Information

CircRNA FGFR3 induces epithelial-mesenchymal transition of ovarian cancer by regulating miR-29a-3p/E2F1 axis.

Publications

CircRNA FGFR3 induces epithelial-mesenchymal transition of ovarian cancer by regulating miR-29a-3p/E2F1 axis.

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