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F-Box and Leucine-Rich Repeat Protein 20 (FBXL20), Negatively Regulated by microRNA (miR)-195-5p, Accelerates the Malignant Progression of Ovarian Cancer

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Abstract

Ovarian cancer (OC) is one of the most common cancers among women, characterized by various histological subtypes. Here, we aimed to investigate the biological function of F-box and leucine-rich repeat protein 20 (FBXL20) in the malignant phenotype of OC cells and its related mechanism. The expression of FBXL20 in OC tissue and normal tissue samples was analyzed through the GEPIA database. Quantitative real-time PCR (qRT-PCR), immunohistochemistry (IHC) and Western blot were employed to detect the expression of miR-195-5p and FBXL20 in OC tissues and cell lines. Cell counting kit-8 (CCK-8) assay, 5-ethynyl-2’-deoxyuridine (EdU) experiment and flow cytometry were applied to detect cell proliferation, cell cycle and apoptosis. Bioinformatics analysis and dual-luciferase reporter gene experiments were adopted to predict and validate the targeting relationship between miR-195-5p and FBXL20 mRNA 3'-untranslated region (3’UTR). Correlation between the expressions of miR-195-5p and FBXL20 mRNA was analyzed by Pearson correlation analysis. FBXL20 expression was upregulated in OC, and its high expression level was significantly associated with higher International Federation of Gynecology and Obstetrics (FIGO) stage and poor tumor differentiation. Functionally, overexpression of FBXL20 promoted proliferation, inhibited apoptosis and accelerated the cell cycle in OC cells in comparison to control group, and knockdown of FBXL20 exerted the opposite effects. Mechanistically, miR-195-5p directly targeted FBXL20 and negatively regulated its expression. Pearson correlation analysis indicated that miR-195-5p was negatively correlated with FBXL20 mRNA expression. In addition, overexpression of miR-195-5p reversed the above biological functions of FBXL20 in OC cells. FBXL20, negatively regulated by miR-195-5p, accelerates the proliferation and cell cycle progression of OC cells, and inhibits cell apoptosis, which might act as a prospective prognostic biomarker and a promising therapeutic target for OC.

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Data Availability

The data used to support the findings of this study are available from the corresponding author upon request.

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Funding

This study is supported by National Natural Science Foundation of Renmin Hospital of Wuhan University.

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Authors and Affiliations

  1. Department of Obstetrics and Gynaecology, Renmin Hospital of Wuhan University, Jiefang Road No.238, Wuhan, 430060, Hubei, China

    Debin Wu, Chen Liu & Li Hong

Authors
  1. Debin Wu
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  2. Chen Liu
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  3. Li Hong
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Contributions

Conceived and designed the experiments: Li Hong; Performed the experiments: Debin Wu, Chen Liu, Li Hong; Analyzed the data: Debin Wu, Chen Liu; Wrote the paper: Debin Wu, Chen Liu, Li Hong. All authors read and approved the final manuscript.

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Correspondence to Li Hong.

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The authors declare that they have no competing interests.

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Our study was approved by the Ethics Review Board of Renmin Hospital of Wuhan University.

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Wu, D., Liu, C. & Hong, L. F-Box and Leucine-Rich Repeat Protein 20 (FBXL20), Negatively Regulated by microRNA (miR)-195-5p, Accelerates the Malignant Progression of Ovarian Cancer. Mol Biotechnol 63, 1235–1243 (2021). https://doi.org/10.1007/s12033-021-00375-y

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  • DOI: https://doi.org/10.1007/s12033-021-00375-y

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