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Down-regulation of lncRNA BLACAT1 inhibits ovarian cancer progression by suppressing the Wnt/β-catenin signaling pathway via regulating miR-519d-3p

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Abstract

Ovarian cancer has the highest mortality in gynecologic malignancies. LncRNA BLACAT1 serves crucial functions in various cancers, but its role in ovarian cancer has not been investigated. In this article, our team explored the role and the potential regulatory mechanism of BLACAT1 in ovarian cancer. Quantitative RT-PCR showed that BLACAT1 was aberrantly up-regulated in ovarian cancer tissues compared with normal tissues. In vitro, BLACAT1 knockdown induced cell cycle arrest and inhibited the proliferation, migration and invasion of ovarian cancer cells using flow cytometry, MTT and EdU assays, wound healing assay and transwell assay, respectively. Luciferase assay verified the binding relationship between microRNA-519d-3p and lncRNA BLACAT1, and BLACAT1 negatively regulated the expression of miR-519d-3p. We also found that miR-519d-3p overexpression could inhibit ovarian cancer cells proliferation, migration and invasion. Further, Western blot demonstrated that the expression of RPS15A and nuclear β-catenin expression was markedly reduced by BLACAT1 knockdown, and cytoplasmic β-catenin level was not obviously affected. In vivo, BLACAT1 knockdown inhibited the tumor growth, and immunohistochemistry showed that ki67 expression was decreased by BLACAT1 suppression. Inhibition of BLACAT1 was sufficient to down-regulate the expression of RPS15A and nuclear β-catenin but did not cause an obvious change in cytoplasmic β-catenin expression. Taken together, BLACAT1 knockdown inhibited the progression of ovarian cancer by suppressing the Wnt/β-catenin signaling pathway via regulating miR-519d-3p. Our work provided a proper understanding of the critical roles of BLACAT1 in ovarian cancer.

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This study was not funded.

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Authors and Affiliations

  1. Department of Ultrasound, Shengjing Hospital of China Medical University, 36 Sanhao Street, Heping District, Shenyang, 110004, Liaoning, People’s Republic of China

    Hua Yang, Xin-lu Wang, Jiao-jiao Gu & Tie-mei Shi

  2. Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, 36 Sanhao Street, Heping District, Shenyang, Liaoning, People’s Republic of China

    Yue Qi

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  1. Hua Yang
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  2. Yue Qi
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  4. Jiao-jiao Gu
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Contributions

Conceptualization: TS; Methodology: HY; Formal analysis and investigation: HY, YQ, XW and JG; Writing original draft preparation: HY; Writing-review and editing: TS.

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Correspondence to Tie-mei Shi.

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All authors have read this manuscript and authorized the submission for publication. All authors declare that there is no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were approved by the Ethics Committee of Shengjing Hospital of China Medical University (Reference Number: 2019PS641K) and in accordance with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. All procedures performed in this study involving animals were in conformity with the Guide for the Care and Use of Laboratory Animals and approved by the Ethical Committee of Shengjing Hospital of China Medical University (Reference Number: 2019PS670K).

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Yang, H., Qi, Y., Wang, Xl. et al. Down-regulation of lncRNA BLACAT1 inhibits ovarian cancer progression by suppressing the Wnt/β-catenin signaling pathway via regulating miR-519d-3p. Mol Cell Biochem 467, 95–105 (2020). https://doi.org/10.1007/s11010-020-03704-y

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  • DOI: https://doi.org/10.1007/s11010-020-03704-y

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