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miR-138在喉癌细胞转移调控中的作用。

Role of miR-138 in the regulation of larynx carcinoma cell metastases.

作者信息

Gao Shang, Wang Jie, Xie Jin, Zhang Tianzhen, Dong Pin

机构信息

Department of Otolaryngology-Head and Neck Surgery, Shanghai First People's Hospital, Shanghai Jiaotong University, 100 Haining Road, Shanghai, 200080, China.

出版信息

Tumour Biol. 2016 Dec;37:15601–15606. doi: 10.1007/s13277-015-4244-y. Epub 2015 Oct 24.

Abstract

The cases of larynx carcinoma (LC) with poor prognosis largely result from the distal metastases of the primary tumor. Since microRNAs (miRNAs) play critical roles during cancer metastases, determination of the involved miRNAs in the regulation of the LC metastases may provide novel therapeutic targets for LC treatment. Here, we studied the LC specimens from the patients and found that the levels of miR-138 were significantly decreased and the levels of ZEB2, a critical factor that regulates cancer cell invasiveness, were significantly increased in LC, compared to the paired normal larynx tissue. Metastatic LC appeared to contained lower levels of miR-138. Moreover, miR-138 and ZEB2 inversely correlated in LC specimens. Bioinformatics analyses showed that miR-138 targeted the 3'-untranslated region (3'-UTR) of ZEB2 mRNA to inhibit its translation, which was confirmed in a luciferase reporter assay. Further, miR-138 overexpression inhibited ZEB2-mediated cell invasiveness, while miR-138 depletion increased ZEB2-mediated cell invasiveness in LC cells. Together, our data suggest that miR-138 suppression in LC cells may promote ZEB2-mediated cancer metastases. Thus, miR-138 appears to be an intriguing therapeutic target to prevent metastases of LC.

摘要

预后较差的喉癌(LC)病例主要是由原发性肿瘤的远处转移所致。由于微小RNA(miRNA)在癌症转移过程中发挥关键作用,因此确定参与调控LC转移的miRNA可能为LC治疗提供新的治疗靶点。在此,我们研究了患者的LC标本,发现与配对的正常喉组织相比,LC中miR-138水平显著降低,而调控癌细胞侵袭性的关键因子ZEB2水平显著升高。转移性LC似乎含有较低水平的miR-138。此外,在LC标本中miR-138与ZEB2呈负相关。生物信息学分析表明,miR-138靶向ZEB2 mRNA的3'-非翻译区(3'-UTR)以抑制其翻译,荧光素酶报告基因检测证实了这一点。此外,miR-138过表达抑制ZEB2介导的细胞侵袭,而miR-138缺失则增加LC细胞中ZEB2介导的细胞侵袭。总之,我们的数据表明,LC细胞中miR-138的抑制可能促进ZEB2介导的癌症转移。因此,miR-138似乎是预防LC转移的一个有吸引力的治疗靶点。

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