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AJUBA通过宫颈癌中的河马通路增加顺铂耐药性。

AJUBA increases the cisplatin resistance through hippo pathway in cervical cancer.

作者信息

Bi Lihong, Ma Feng, Tian Rui, Zhou Yanli, Lan Weiguang, Song Quanmao, Cheng Xiankui

机构信息

Department of Gynecology, PKUCare Luzhong Hospital, Zibo, Shandong, China.

Department of Oncology, PKUCare Luzhong Hospital, Zibo, Shandong, China.

出版信息

Gene. 2018 Feb 20;644:148-154. doi: 10.1016/j.gene.2017.11.017. Epub 2017 Nov 7.

Abstract

Though LIM-domain protein AJUBA was identified as a putative oncogene, the function and underlying mechanisms of AJUBA in cervical cancer remain largely unknown. Firstly, AJUBA expression was detected via real-time quantitative PCR in patients' samples. Furthermore, Hela and Siha cells were transfected with AJUBA-overexpressing plasmids, and then exposed to cisplatin, the apoptosis was measured by cytometry assay. In addition, the expression of YAP and TAZ was disclosed through western blot assay. Our results revealed that AJUBA expression was significantly higher in the cervical cancer patients resistant to cisplatin treatment compared with cervical cancer patients sensitive to cisplatin treatment. In addition, overall survival time was significantly shorter in the cervical cancer patients with high AJUBA expression compare with those with low AJUBA expression using kaplan-meier analysis. Hela and Siha cells transfected with AJUBA-expressing plasmids exposed to cisplatin treatment had higher survival rate compared with the cells transfected with empty vector control. Mechanistic studies revealed the AJUBA upregulated the downstream targets YAP and TAZ. These results suggest that high AJUBA level enhances cervical cancer cells drug resistance to cisplatin, also associates with decreased patient survival times.

摘要

尽管LIM结构域蛋白AJUBA被鉴定为一种假定的癌基因,但AJUBA在宫颈癌中的功能及潜在机制仍 largely未知。首先,通过实时定量PCR检测患者样本中AJUBA的表达。此外,用AJUBA过表达质粒转染Hela和Siha细胞,然后使其暴露于顺铂,通过细胞计数法检测细胞凋亡情况。另外,通过蛋白质印迹法揭示YAP和TAZ的表达。我们的结果显示,与对顺铂治疗敏感的宫颈癌患者相比,对顺铂治疗耐药的宫颈癌患者中AJUBA表达显著更高。此外,使用Kaplan-Meier分析,AJUBA高表达的宫颈癌患者的总生存时间明显短于AJUBA低表达的患者。与用空载体对照转染的细胞相比,用表达AJUBA的质粒转染的Hela和Siha细胞在接受顺铂治疗后具有更高的存活率。机制研究表明,AJUBA上调下游靶点YAP和TAZ。这些结果表明,高AJUBA水平增强了宫颈癌细胞对顺铂的耐药性,也与患者生存时间缩短有关。

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