Department of Radiation Oncology, Peking University Third Hospital, Beijing 100191, China.
Radiat Oncol. 2010 Nov 1;5:100. doi: 10.1186/1748-717X-5-100.
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.
miRNA-17-92（miRNA-17-92）簇位于 13q31-q32 染色体上，也称为癌 miRNA-1，由七个 miRNA 组成，作为多顺反子转录单位转录。miRNA-17-92 的过表达已在淋巴瘤和其他实体瘤中观察到。到目前为止，miRNA-17-92 的表达是否影响肿瘤细胞对放射治疗的反应尚未得到解决。在本研究中，我们研究了 miRNA-17-92 对人套细胞淋巴瘤（MCL）细胞 Z138c 放射敏感性的影响。过表达 miRNA-17-92 显著增加了不同剂量照射后人类 MCL 细胞的存活细胞数量、细胞增殖，并降低了细胞死亡。免疫印迹分析显示，过表达 miRNA-17-92 后，在照射后的 MCL 细胞中，磷酸酶和张力同源物（PTEN）和 PHLPP2 下调，pAkt 活性增强。这些发现是 miRNA-17-92 簇过表达显著增加人类 MCL 细胞放射抗性的第一个直接证据，为改善 MCL 的放射治疗提供了新的靶分子。
