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Downregulation of lncRNA XIST Represses Tumor Growth and Boosts Radiosensitivity of Neuroblastoma via Modulation of the miR-375/L1CAM Axis

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Abstract

Neuroblastoma (NB) is a heterogeneous tumor that is common in infants and young children. Long non-coding RNA X-inactive specific transcript (XIST) is implicated in NB advancement. Nevertheless, the role and regulatory mechanism by which XIST in NB are not fully elucidated. Expression levels of XIST, microRNA-375-5p (miR-375), and L1 cell adhesion molecular (L1CAM) were examined through quantitative real-time polymerase chain reaction (qRT-PCR). The cell cycle progression, proliferation, and colony formation of NB cells were determined with flow cytometry, 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT), or cell colony formation assays. Cell apoptotic rate was detected with flow cytometry assay. The relationship between XIST or L1CAM and miR-375 was verified via dual-luciferase reporter assay. The level of L1CAM protein was examined through western blotting. The role of XIST in vivo was confirmed through xenograft assay. XIST and L1CAM were upregulated while miR-375 was downregulated in NB tissues and cells. XIST depletion repressed tumor growth in vivo and elevated radiosensitivity, arrested cell cycle progression, and impeded proliferation of NB cells in vitro. Mechanistically, XIST modulated L1CAM expression through competitively binding to miR-375. Furthermore, miR-375 inhibitor recovered XIST inhibition-mediated effects on the radiosensitivity and malignant behaviors of NB cells. Also, L1CAM overexpression reversed the effects of miR-375 enhancement on the cell cycle progression, proliferation, and radiosensitivity of NB cells. XIST downregulation repressed tumor growth and boosted radiosensitivity of NB via modulating the miR-375/L1CAM axis, indicating that XIST was a promising target for NB treatment.

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Author notes

  1. Haiyan Yang and Xiao Zhang have contributed equally.

Authors and Affiliations

  1. Department of Pediatric, Affiliated Hospital of Weifang Medical University, Weifang, 261031, Shandong, China

    Haiyan Yang, Xiao Zhang, Yuehua Zhao, Jian Zhang, Yiwen Gao, Qian Liu & Wenhua Zhang

  2. Department of Obstetrics, Weifang People’s Hospital, Weifang, 261000, Shandong, China

    GuoLi Sun

  3. School of Marxism, Weifang Medical University, No.7166, Baotong West Street, Weifang, 261053, Shandong, China

    Hongjin Zhu

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  1. Haiyan Yang
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Yang, H., Zhang, X., Zhao, Y. et al. Downregulation of lncRNA XIST Represses Tumor Growth and Boosts Radiosensitivity of Neuroblastoma via Modulation of the miR-375/L1CAM Axis. Neurochem Res 45, 2679–2690 (2020). https://doi.org/10.1007/s11064-020-03117-9

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  • DOI: https://doi.org/10.1007/s11064-020-03117-9

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