MicroRNA-17-92 significantly enhances radioresistance in human mantle cell lymphoma cells.
MicroRNA-17-92 significantly enhances radioresistance in human mantle cell lymphoma cells.
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DOI：
10.1186/1748-717x-5-100
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发表时间：
2010-11-01
期刊：
影响因子：
--
通讯作者：
Wang JJ
中科院分区：
文献类型：
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作者：
Jiang P;Rao EY;Meng N;Zhao Y;Wang JJ
microRNA-17-92（miRNA-17-92）簇位于染色体13 q31-q32，也称为oncomir-1，由7个转录为多顺反子单位的miRNA组成。已经在淋巴瘤和其他实体瘤中观察到miRNA-17-92的过表达。miRNA-17-92的表达是否影响肿瘤细胞对放射治疗的反应迄今尚未解决。在本研究中，我们研究了miRNA-17-92对人套细胞淋巴瘤（MCL）细胞Z138 c放射敏感性的影响。miRNA-17-92的过表达显著增加了不同剂量辐射后人MCL细胞的存活细胞数、细胞增殖和减少细胞死亡。免疫印迹分析显示，在照射后过表达miRNA-17-92的MCL细胞中，磷酸酶和张力同源物（PTEN）和PHLPP 2表达下调，pAkt活性增强。这些发现首次直接证明过表达miRNA-17-92簇可显著增加人MCL细胞的放射抗性，为临床改善MCL的放射治疗提供了新的靶分子。
The microRNA-17-92 (miRNA-17-92) cluster, at chromosome 13q31-q32, also known as oncomir-1, consists of seven miRNAs that are transcribed as a polycistronic unit. Over-expression of miRNA-17-92 has been observed in lymphomas and other solid tumors. Whether miRNA-17-92 expression affects the response of tumor cells to radiotherapy is not addressed so far. In the present study, we studied the effects of miRNA-17-92 on the radiosensitivity of human mantle cell lymphoma (MCL) cells Z138c. Over-expression of miRNA-17-92 significantly increased survival cell number, cell proliferation and decreased cell death of human MCL cells after different doses of radiation. Immunoblot analysis showed that phosphatase and tension homolog (PTEN) and PHLPP2 was down-modulated and pAkt activity was enhanced in MCL cells after over-expressing miRNA-17-92 after irradiation. These findings are the first direct evidence that over-expression of miRNA-17-92 cluster significantly increases the radioresistance of human MCL cells, which offers a novel target molecule for improving the radiotherapy of MCL in clinic.