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microRNA-124 inhibits stem-like properties and enhances radiosensitivity in nasopharyngeal carcinoma cells via direct repression of expression of JAMA.
Journal of Cellular and Molecular Medicine ( IF 4.3 ) Pub Date : 2020-07-17 , DOI: 10.1111/jcmm.15177
Yunhong Tian 1 , Yunming Tian 2 , Yinuo Tu 1 , Guoqian Zhang 1 , Xing Zeng 1 , Jie Lin 1 , Meiling Ai 1 , Zixu Mao 3 , Ronghui Zheng 1 , Yawei Yuan 1
Affiliation  

Cancer stem cells (CSCs) are a source of tumour recurrence in patients with nasopharyngeal carcinoma (NPC); however, the function of microRNA‐124 (miR‐124) in NPC CSCs has not been clearly defined. In this study, we investigated the role of miR‐124 in NPC CSCs. qRT‐PCR was performed to measure miR‐124 expression in NPC tissues and cell lines and the effects of miR‐124 on stem‐like properties and radiosensitivity of NPC cells measured. Luciferase reporter assays and rescue experiments were used to investigate the interaction of miR‐124 with the 3′UTR of junctional adhesion molecule A (JAMA). Finally, we examined the effects of miR‐124 in an animal model and clinical samples. Down‐regulation of miR‐124 was detected in cancer tissues and was inversely associated with tumour stage and lymph node metastasis. Overexpression of miR‐124 inhibited stemness properties and enhanced radiosensitivity of NPC cells in vitro and in vivo via targeting JAMA. Up‐regulation of miR‐124 was correlated with superior overall survival of patients with NPC. Our study demonstrates that miR‐124 can inhibit stem‐like properties and enhance radiosensitivity by directly targeting JAMA in NPC. These findings provide novel insights into the molecular mechanisms underlying therapy failure in NPC.

中文翻译:

microRNA-124通过直接抑制JAMA的表达来抑制干细胞样特性并增强鼻咽癌细胞的放射敏感性。

癌症干细胞(CSCs)是鼻咽癌(NPC)患者肿瘤复发的来源。但是,尚未明确定义microRNA-124(miR-124)在NPC CSC中的功能。在这项研究中,我们调查了miR-124在NPC CSC中的作用。进行了qRT-PCR来测量NPC组织和细胞系中miR-124的表达以及miR-124对NPC细胞的茎样性质和放射敏感性的影响。萤光素酶报告基因检测和拯救实验用于研究miR-124与结合黏附分子A(JAMA)3'UTR的相互作用。最后,我们检查了miR-124在动物模型和临床样品中的作用。在癌症组织中检测到miR-124的下调,与肿瘤分期和淋巴结转移呈负相关。通过靶向JAMA,miR‐124的过表达抑制了NPC细胞的干性和增强的NPC细胞的放射敏感性。miR-124的上调与NPC患者的总生存期长有关。我们的研究表明,miR-124可通过直接靶向NPC中的JAMA抑制茎样性质并增强放射敏感性。这些发现为NPC治疗失败的分子机制提供了新颖的见解。
更新日期:2020-07-17
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