MiR-497 decreases cisplatin resistance in ovarian cancer cells by targeting mTOR/P70S6K1
MiR-497 decreases cisplatin resistance in ovarian cancer cells by targeting mTOR/P70S6K1
复制标题
MiR-497 通过靶向 mTOR/P70S6K1 降低卵巢癌细胞的顺铂耐药性
DOI：
10.18632/oncotarget.4762
复制
发表时间：
2015-09-22
期刊：
影响因子：
--
通讯作者：
Chen, Ke
中科院分区：
文献类型：
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作者：
Xu, Shaohua;Fu, Guang-Bo;Chen, Ke
卵巢癌顺铂耐药的机制尚不清楚。在本研究中，我们发现miR-497在化疗耐药的卵巢癌细胞和肿瘤组织中的表达水平由于miR-497启动子的高甲基化而降低。低miR-497表达水平与卵巢癌化疗耐药表型相关。通过分析临床基因表达阵列数据集中miR-497、mTOR和p70 S6 K1的表达水平，我们发现mTOR和p70 S6 K1这两种与多种类型人类癌症化疗耐药相关的蛋白质与卵巢癌组织中miR-497水平呈负相关。通过使用原位卵巢肿瘤模型和Tet-On诱导的miR-497表达系统，我们的结果表明miR-497的过表达使耐药卵巢肿瘤对顺铂治疗敏感。因此，我们建议miR-497可用作治疗补充剂，以增加卵巢癌对顺铂的治疗反应。
The mechanism of cisplatin resistance in ovarian cancer is not clearly understood. In the present investigation, we found that the expression levels of miR-497 were reduced in chemotherapy-resistant ovarian cancer cells and tumor tissues due to hypermethylation of miR-497 promoter. Low miR-497 expression levels were associated with chemo-resistant phonotype of ovarian cancer. By analyzing the expression levels of miR-497, mTOR and p70S6K1 in a clinical gene-expression array dataset, we found that mTOR and p70S6K1, two proteins correlated to chemotherapy-resistance in multiple types of human cancers, were inversely correlated with miR-497 levels in ovarian cancer tissues. By using an orthotopic ovarian tumor model and a Tet-On inducible miR-497 expression system, our results demonstrated that overexpression of miR-497 sensitizes the resistant ovarian tumor to cisplatin treatment. Therefore, we suggest that miR-497 might be used as a therapeutic supplement to increase ovarian cancer treatment response to cisplatin.