Downregulation of lncRNA XIST Represses Tumor Growth and Boosts Radiosensitivity of Neuroblastoma via Modulation of the
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ORIGINAL PAPER
Downregulation of lncRNA XIST Represses Tumor Growth and Boosts Radiosensitivity of Neuroblastoma via Modulation of the miR‑375/ L1CAM Axis Haiyan Yang1 · Xiao Zhang1 · Yuehua Zhao1 · GuoLi Sun2 · Jian Zhang1 · Yiwen Gao1 · Qian Liu1 · Wenhua Zhang1 · Hongjin Zhu3 Received: 11 May 2020 / Revised: 5 August 2020 / Accepted: 15 August 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
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-dimethylthiazol2-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. Keywords NB · XIST · miR-375 · L1CAM · Radiosensitivity
Introduction Neuroblastoma (NB) is a solid tumor that originates from neural crest cells of the sympathetic nervous system. It usually occurs in children under 5 years of age and is common in the neck, abdomen, adrenal glands, chest, and pelvic cavity Haiyan Yang and Xiao Zhang have contributed equally. * Hongjin Zhu [email protected] 1
Department of Pediatric, Affiliated Hospital of Weifang Medical University, Weifang 261031, Shandong, China
2
Department of Obstetrics, Weifang People’s Hospital, Weifang 261000, Shandong, China
3
School of Marxism, Weifang Medical University, No.7166, Baotong West Street, Weifang 261053, Shandong, China
[1]. Also, NB is highly aggressive, accounting for 15% and 7% of childhood cancer deaths and childhood malignancies, respectively [2]. NB has a multi-model cli
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