MicroRNA-24 induces cisplatin resistance by targeting PTEN in human tongue squamous cell carcinoma.
MicroRNA-24 induces cisplatin resistance by targeting PTEN in human tongue squamous cell carcinoma.
复制标题
MicroRNA-24 通过靶向人舌鳞状细胞癌中的 PTEN 诱导顺铂耐药。
DOI：
10.1016/j.oraloncology.2015.08.002
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发表时间：
2015-11
期刊：
影响因子：
4.8
通讯作者：
Li Yigong
中科院分区：
文献类型：
--
作者：
Zheng Xiangqian;Li Jiansen;Peng Chen;Zhao Jingzhu;Chi Jiadong;Meng Xiangrui;Yun Xinwei;Li Dapeng;Yu Yang;Gao Ming;Li Yigong
研究背景miR-24是舌鳞状细胞癌（tongue squamous cell carcinoma，TSCC）中表达上调最显著的miRNAs之一。PTEN在多种癌症的细胞存活和顺铂耐药性中发挥重要作用。方法/主要发现本研究采用实时荧光定量PCR方法检测79例配对TSCC组织和8株TSCC细胞系中miR-24的表达，并分析其与临床病理参数的相关性。此外，我们发现miR-24的失调与高级别和晚期肿瘤相关。此外，miR-24通过靶向PTEN的3′-UTR区域，下调PTEN蛋白表达，激活Akt促生存通路，从而诱导细胞存活和顺铂耐药。我们的研究结果表明，miR-24的失调是人舌鳞状细胞癌中的复发事件，与肿瘤进展相关，24主要通过靶向PTEN/Akt途径诱导细胞存活和顺铂抗性。因此，miR-24可能是干预这种恶性肿瘤的重要靶点。
BackgroundmiR-24 is one of the most significantly up-regulated miRNAs in tongue squamous cell carcinoma (TSCC). PTEN plays an important role in the cell survival and cisplatin resistance of multiple cancers. However, it remains unclear what role does function and mechanism of miR-24 and PTEN play in TSCC.Methodology/principal findingsIn this study, miR-24 expression was detected in 79 cases of paired TSCC and normal tissues and 8 TSCC cell lines by real-time PCR and the relevance between miR-24 expression and clinicopathological parameters were analyzed. Further, we demonstrated that deregulation of miR-24 was found to associate with high grade and late stage tumor. In addition, miR-24 induces cell survival and cisplatin resistance through targeting 3′-UTR region of the PTEN, which leads to downregulation of PTEN protein and activation of Akt pro-survival pathway.Conclusions/significanceIn conclusion, our results demonstrated that deregulation of miR-24 is a recurrent event in human tongue squamous cell carcinoma and associate with tumor progression and that miR-24 induces cell survival and cisplatin resistance primarily through targeting PTEN/Akt pathway. Thus, miR-24 could be important targets for intervention of this malignancy.
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DOI：
10.1146/annurev.pathol.4.110807.092222
发表时间：
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期刊：
Annual review of pathology
影响因子：
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作者：
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通讯作者：
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影响因子：
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10.1002/9781118300312.ch14
发表时间：
2013-11
期刊：
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影响因子：
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作者：
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DOI：
10.1007/978-3-319-11985-4_10
发表时间：
2014
期刊：
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影响因子：
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作者：
A. Evangelista;M. Marques
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A. Evangelista;M. Marques