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微小RNA-18a下调DICER1并促进鼻咽癌的增殖和转移。

miR-18a downregulates DICER1 and promotes proliferation and metastasis of nasopharyngeal carcinoma.

作者信息

Chen Xi, Wang Juan, Cheng Lei, Lu Mei-Ping

机构信息

Department of Otorhinolaryngology, The First Affiliated Hospital, Nanjing Medical University Nanjing, China.

Department of Otorhinolaryngology, The Affiliated Jiangning Hospital of Nanjing Medical University Nanjing, China.

出版信息

Int J Clin Exp Med. 2014 Apr 15;7(4):847-55. eCollection 2014.

Abstract

Nasopharyngeal carcinoma, common in Southeast Asia and the southern provinces of China, often has metastasized by the time of diagnosis; thus there exists the need for improved diagnosis and treatment. Accumulating evidence indicates that microRNAs (miRNAs), which post-transcriptionally regulate protein expression, contribute to the processes of tumorigenesis, including metastasis and cellular invasion. Here, we studied the effect of one miRNA, miR-18a-which is believed to target the miRNA-processing enzyme DICERl-on nasopharyngeal carcinoma. In situ hybridization revealed that miR-18a was more highly expressed in nasopharyngeal carcinoma tissues than in control tissues (P < 0.05), and the overexpression correlated with clinical stage and lymph node metastasis (P < 0.05), but not with age and gender (P > 0.05). In vitro analysis of HK1 nasopharyngeal carcinoma cells transfected with miR-18a exhibited significantly decreased expression of DICER1 mRNA and protein but significantly increased proliferation and invasion properties compared to control cells (P < 0.05). Finally, nude mice injected with miR-18a transfected-HK1 cells displayed significantly increased tumor growth and lung metastasis in vivo (P < 0.05). These findings suggest that miR-18a expression can promote proliferation and metastasis of nasopharyngeal carcinoma cells and that these activities may occur through its regulation of DICER1.

摘要

鼻咽癌在东南亚和中国南方省份较为常见,通常在确诊时就已发生转移;因此,需要改进诊断和治疗方法。越来越多的证据表明,在转录后调节蛋白质表达的微小RNA(miRNA)参与了肿瘤发生过程,包括转移和细胞侵袭。在此,我们研究了一种miRNA,即miR-18a(据信靶向miRNA加工酶DICER1)对鼻咽癌的影响。原位杂交显示,miR-18a在鼻咽癌组织中的表达高于对照组织(P < 0.05),且这种过表达与临床分期和淋巴结转移相关(P < 0.05),但与年龄和性别无关(P > 0.05)。与对照细胞相比,对转染了miR-18a的HK1鼻咽癌细胞进行的体外分析显示,DICER1 mRNA和蛋白的表达显著降低,但增殖和侵袭能力显著增强(P < 0.05)。最后,注射了转染miR-18a的HK1细胞的裸鼠在体内显示出肿瘤生长和肺转移显著增加(P < 0.05)。这些发现表明,miR-18a的表达可促进鼻咽癌细胞的增殖和转移,且这些活动可能是通过其对DICER1的调节而发生的。

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