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微小RNA-101通过靶向CXC趋化因子受体7在口腔鳞状细胞癌中发挥肿瘤抑制作用。

miRNA-101 acts as a tumor suppressor in oral squamous cell carcinoma by targeting CX chemokine receptor 7.

作者信息

Hui Yuan, Li Yu, Jing Yan, Feng Jian-Q, Ding Yin

机构信息

State Key Laboratory of Military Stomatology, Department of Orthodontics, School of Stomatology, Fourth Military Medical University Xi'an 710032, Shaanxi, PR China.

Department of Stomatology, General Hospital of Jinan Military Command Jinan 250031, PR China.

出版信息

Am J Transl Res. 2016 Nov 15;8(11):4902-4911. eCollection 2016.

PMID:27904690
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5126332/
Abstract

miR-101 is significantly downregulated in various human cancers, including oral squamous cell carcinoma (OSCC). However, the role of miR-101 in OSCC has not been elucidated. In this study, miR-101 lowly expressed in OSCC tissues and cell lines compared with that in adjacent normal tissues and human normal oral keratinocyte cells. Bioinformatics analysis predicted that miR-101 could potentially target CX chemokine receptor 7 (CXCR7), a promoter of tumor development, to attenuate OSCC progression. Restoring miR-101 expression in OSCC cells suppressed cell proliferation, invasion, and migration. The ectopic expression of CXCR7 in OSCC cells overexpressing miR-101 restored the proliferation and motility capabilities abolished by miR-101. The inhibitory effects of miR-101 on OSCC growth and metastasis were mimicked by CXCR7 knockdown in vivo. CXCR7 expression was upregulated in OSCC tissues. The high expression level of CXCR7 was negatively correlated with miR-101 level and poor prognosis of patients with OSCC. Overall, miR-101 exerts tumor-suppressive functions by targeting CXCR7, leading to inhibition of OSCC cell growth, invasion, and migration. Hence, miR-101 may be a potential target for OSCC diagnosis and therapeutic applications.

摘要

微小RNA-101(miR-101)在包括口腔鳞状细胞癌(OSCC)在内的多种人类癌症中显著下调。然而,miR-101在OSCC中的作用尚未阐明。在本研究中,与相邻正常组织和人正常口腔角质形成细胞相比,miR-101在OSCC组织和细胞系中低表达。生物信息学分析预测,miR-101可能靶向肿瘤发展的促进因子CXC趋化因子受体7(CXCR7),以减弱OSCC的进展。在OSCC细胞中恢复miR-101的表达可抑制细胞增殖、侵袭和迁移。在过表达miR-101的OSCC细胞中CXCR7的异位表达恢复了被miR-101消除的增殖和运动能力。在体内,CXCR7基因敲低模拟了miR-101对OSCC生长和转移的抑制作用。CXCR7在OSCC组织中表达上调。CXCR7的高表达水平与miR-101水平及OSCC患者的不良预后呈负相关。总体而言,miR-101通过靶向CXCR7发挥肿瘤抑制功能,导致OSCC细胞生长、侵袭和迁移受到抑制。因此,miR-101可能是OSCC诊断和治疗应用的潜在靶点。

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