microRNA-124 inhibits stem-like properties and enhances radiosensitivity in nasopharyngeal carcinoma cells via direct repression of expression of JAMA.

microRNA-124 inhibits stem-like properties and enhances radiosensitivity in nasopharyngeal carcinoma cells via direct repression of expression of JAMA.
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microRNA-124通过直接抑制JAMA的表达抑制干细胞样特性并增强鼻咽癌细胞的放射敏感性

DOI:
10.1111/jcmm.15177
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发表时间:
2020-09
影响因子:
5.3
通讯作者:
Yuan Y
Yuan Y
中科院分区:
医学2区
文献类型:
--
作者:
Tian Y;Tian Y;Tu Y;Zhang G;Zeng X;Lin J;Ai M;Mao Z;Zheng R;Yuan Y

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肿瘤干细胞(CSCs)是鼻咽癌患者肿瘤复发的来源之一,然而,microRNA-124(miR-124)在鼻咽癌CSCs中的作用尚不清楚。在本研究中,我们研究了miR-124在鼻咽癌干细胞中的作用。采用定量逆转录聚合酶链式反应检测miR-124在鼻咽癌组织和细胞系中的表达,并检测miR-124对鼻咽癌细胞的干细胞样特性和放射敏感性的影响。通过荧光素酶报告实验和挽救实验研究miR-124与JAMA 3‘端非编码区的相互作用。最后,我们在动物模型和临床样本中检验了miR-124的作用。MiR-124在癌组织中表达下调,且与肿瘤分期和淋巴结转移呈负相关。通过靶向JAMA,miR-124过表达抑制了鼻咽癌细胞的干性特性,并在体内外增强了鼻咽癌细胞的放射敏感性。MiR-124的上调与鼻咽癌患者的总体生存优势相关。我们的研究表明miR-124可以通过直接靶向JAMA在鼻咽癌中抑制干细胞样特性并增强放射敏感性。这些发现为鼻咽癌治疗失败的分子机制提供了新的见解。
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.
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