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microRNA-200a 通过靶向 CD47 促进巨噬细胞吞噬作用并抑制鼻咽癌细胞增殖、迁移和侵袭

MicroRNA-200a Promotes Phagocytosis of Macrophages and Suppresses Cell Proliferation, Migration, and Invasion in Nasopharyngeal Carcinoma by Targeting CD47.

机构信息

Department of Otolaryngology-Head and Neck Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Department of Otolaryngology-Head and Neck Surgery, The Third Affiliated Hospital of Southern Medical University, Southern Medical University, Guangzhou, China.

出版信息

Biomed Res Int. 2020 Feb 20;2020:3723781. doi: 10.1155/2020/3723781. eCollection 2020.

Abstract

Nasopharyngeal carcinoma (NPC) causes severe oncogenic lesions in the nasopharynx. CD47, a transmembrane integrin-associated protein, plays a key role in the ability of tumor cells to escape phagocytosis, working as an immune checkpoint in the immune response. Besides this role, CD47 has been reported to regulate cell proliferation and migration. The present study addresses the relationship between CD47 and microRNA-200a and examines their regulatory mechanisms in NPC. Bioinformatics analyses and dual-luciferase reporter assays were used to confirm the putative relationship between miR-200a and CD47, and their interaction was further detected using western blotting and RT-PCR. Further, results showed that miR-200a affect NPC cell proliferation, migration, and invasion by regulating CD47. A cell phagocytosis assay showed that miR-200a and a CD47 monoclonal antibody increased the sensitivity of NPC cells to macrophage phagocytosis by inhibiting the functions of CD47. Additionally, miR-200a expression was suppressed and CD47 expression increased in both clinical NPC tissues and cell lines. Taken together, these results show the miR-200a/CD47 combination as a potential therapeutic for treatment of NPC.

摘要

鼻咽癌(NPC)可导致鼻咽部严重的致癌病变。CD47 是一种跨膜整合素相关蛋白,在肿瘤细胞逃避吞噬作用的能力中发挥关键作用,作为免疫反应中的免疫检查点。除了这种作用外,CD47 还被报道可调节细胞增殖和迁移。本研究探讨了 CD47 与 microRNA-200a 之间的关系,并研究了它们在 NPC 中的调节机制。生物信息学分析和双荧光素酶报告基因实验用于证实 miR-200a 与 CD47 之间的假定关系,并通过 Western blot 和 RT-PCR 进一步检测它们的相互作用。进一步的结果表明,miR-200a 通过调节 CD47 影响 NPC 细胞的增殖、迁移和侵袭。细胞吞噬实验表明,miR-200a 和 CD47 单克隆抗体通过抑制 CD47 的功能增加 NPC 细胞对巨噬细胞吞噬的敏感性。此外,miR-200a 的表达在临床 NPC 组织和细胞系中受到抑制,而 CD47 的表达增加。总之,这些结果表明 miR-200a/CD47 组合可能成为 NPC 治疗的潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6242/7054800/806ef4efeb42/BMRI2020-3723781.001.jpg

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