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MiR-30a suppresses clear cell renal cell carcinoma proliferation and metastasis by targeting LRP6

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Abstract

Recently, the role of miR-30a in tumor development has attracted extensive attention. In this study, we aimed to elucidate the role of miR-30a and its associated target low-density lipoprotein receptor-related protein 6 (LRP6) in clear cell renal cell carcinoma (ccRCC) cells. Here, miR-30a was markedly down-regulated in ccRCC tissues and cells, and was correlated with the advanced TNM stage and poor prognosis. By contrast, LRP6 protein level was increased in ccRCC specimens and cell lines, and inversely correlated with miR-30a expression. Stable overexpression of miR-30a suppressed cell proliferation in vitro, impeded tumor growth in vivo, prevented migration and invasion, and triggered apoptosis of ccRCC cells. Also, over-expression of miR-30a in ccRCC cells promoted the expression of the epithelial marker E-cadherin and reduced the levels of mesenchymal markers. Mechanistically, the dual-luciferase reporter, RNA immunoprecipitation and western blot assays confirmed that miR-30a directly targeted the 3′-untranslated regions of LRP6 to inhibit its expression. Further, miR-30a-mediated effect was partially reversed by co-transfection with LRP6 plasmids or enhanced by silencing of LRP6. In conclusion, miR-30a exhibits effective antitumor properties by targeting LRP6 in proliferation and metastasis of ccRCC. This study could provide new insights into the treatment of ccRCC.

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Authors and Affiliations

  1. Department of Spine Surgery, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Jinan, Shandong, China

    Yanjun Ren

  2. Department of Ultrasound, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Jinan, Shandong, China

    Li Zhang

  3. Department of Intensive Care Unit, Shandong Provincial Third Hospital, Cheeloo College of Medicine, Shandong University, No.11, Central Wuying Hill Road, Jinan, 250031, Shandong, China

    Wei Zhang & Yikai Gao

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  1. Yanjun Ren
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  2. Li Zhang
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  3. Wei Zhang
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  4. Yikai Gao
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Correspondence to Yikai Gao.

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The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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The human study was approved by the Ethics Committee of Shandong Provincial Third Hospital (SLSY-H-201714). All the samples were collected with written informed consent in accordance with the Declaration of Helsinki. All experimental animal procedures in this study conformed to the National Institutes of Health Guide for the Care and Use of Laboratory Animals, and were approved by the Institutional Animal Care and Use Committee of Shandong Provincial Third Hospital (SLSY-A-201803).

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Ren, Y., Zhang, L., Zhang, W. et al. MiR-30a suppresses clear cell renal cell carcinoma proliferation and metastasis by targeting LRP6. Human Cell 34, 598–606 (2021). https://doi.org/10.1007/s13577-020-00472-1

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  • DOI: https://doi.org/10.1007/s13577-020-00472-1

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