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

• Authors: Yunhong Tian, Guangzhou Medical University; Yunming Tian, Hui Zhou Municipal Cent Hosp; Yinuo Tu, Guangzhou Medical University; Guoqian Zhang, Guangzhou Medical University; Xing Zeng, Guangzhou Medical University; Jie Lin, Guangzhou Medical University; Meiling Ai, Guangzhou Medical University; Zixu Mao, Emory University; Ronghui Zheng, Guangzhou Medical University; Yawei Yuan, Guangzhou Medical University
• Journal Title: JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
• Volume: Volume 24, Number 17
• Publisher: WILEY | 2020-07-17, Pages 9533-9544
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1111/jcmm.15177
• Subjects: Biology, Cell; Biology, Molecular; Health Sciences, Oncology
• Keywords: Science & Technology; Life Sciences & Biomedicine; Cell Biology; Medicine, Research & Experimental; Research & Experimental Medicine; junctional adhesion molecule A; microRNA-124; nasopharyngeal carcinoma; stem-like properties; EPITHELIAL-MESENCHYMAL TRANSITION; JUNCTIONAL ADHESION MOLECULE; DIFFERENTIATION; METASTASIS; POPULATION; MIGRATION; MARKER

Abstract

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.