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微小RNA-140通过靶向趋化因子受体4抑制鼻咽癌的肿瘤进展。

MicroRNA-140 inhibits tumor progression in nasopharyngeal carcinoma by targeting CXCR4.

作者信息

Yao Chengyun, Huang Shengfu, Wu Jianfeng, Yin Li, Jiang Xuesong, Chen Cheng, Wu Wenlan, Xu Jianhua, He Xia

机构信息

Department of Radiotherapy, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing Medical University Affiliated Cancer Hospital Nanjing 210009, China.

Head and Neck Surgery, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing Medical University Affiliated Cancer Hospital Nanjing 210009, China.

出版信息

Int J Clin Exp Pathol. 2017 Jul 1;10(7):7750-7759. eCollection 2017.

Abstract

Recent evidence has indicated that miRNAs play important roles in carcinogenesis. The identification of dysregulated miRNAs and the target genes they regulate might enhance our understanding of the molecular mechanisms of nasopharyngeal carcinoma (NPC). microRNA-140 (miR-140) has been found to be down-regulated in cancer. However its role in nasopharyngeal carcinoma remains unclear. CXCR4 was predicted to be the target gene of miR-140. The current research was designed to delineate the mechanism of miR-140 in regulating NPC via targeting CXCR4. In this study, miR-140 was underexpressed in NPC tissues and cell lines compared with their normal controls and the biological function and direct target genes of miR-140 in NPC cells were investigated. Importantly, we demonstrate that the over expression of miR-140 significantly inhibits NPC cell proliferation and induces apoptosis. Additionally, CXCR4 was predicted the target gene of miR-140 and the luciferase reporter assay revealed that miR-140 was directly bound to the 3'-UTR of CXCR4. Furthermore, CXCR4 was inversely correlated with the expression of miR-140 in NPC cells. Taken together, our results suggest miR-140 suppresses tumor proliferation and induces apoptosis by inhibiting CXCR4, which might provide a new insight into the molecular mechanisms that regulate the development and progression of NPC, and it provides novel therapeutic targets for NPC.

摘要

近期证据表明,微小RNA(miRNA)在肿瘤发生过程中发挥重要作用。鉴定失调的miRNA及其调控的靶基因可能会增进我们对鼻咽癌(NPC)分子机制的理解。已发现微小RNA - 140(miR - 140)在癌症中表达下调。然而,其在鼻咽癌中的作用仍不清楚。CXCR4被预测为miR - 140的靶基因。当前研究旨在阐明miR - 140通过靶向CXCR4调控鼻咽癌的机制。在本研究中,与正常对照相比,miR - 140在鼻咽癌组织和细胞系中表达不足,并对miR - 140在鼻咽癌细胞中的生物学功能和直接靶基因进行了研究。重要的是,我们证明miR - 140的过表达显著抑制鼻咽癌细胞增殖并诱导凋亡。此外,CXCR4被预测为miR - 140的靶基因,荧光素酶报告基因检测显示miR - 140直接与CXCR4的3'-非翻译区(3'-UTR)结合。此外,CXCR4与鼻咽癌细胞中miR - 140的表达呈负相关。综上所述,我们的结果表明miR - 140通过抑制CXCR4来抑制肿瘤增殖并诱导凋亡,这可能为调控鼻咽癌发生和发展的分子机制提供新的见解,并为鼻咽癌提供新的治疗靶点。

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