miR-375 is upregulated in acquired paclitaxel resistance in cervical cancer.
miR-375 is upregulated in acquired paclitaxel resistance in cervical cancer.
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miR-375在宫颈癌获得性紫杉醇耐药中上调
DOI：
10.1038/bjc.2013.308
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发表时间：
2013-07-09
影响因子：
8.8
通讯作者：
Xie X
中科院分区：
文献类型：
--
作者：
Shen Y;Wang P;Li Y;Ye F;Wang F;Wan X;Cheng X;Lu W;Xie X
背景：化疗耐药是导致癌症死亡的关键因素之一，新的证据表明microRNAs（miRNAs）在调节癌症化疗敏感性中起着关键作用。方法：应用微阵列技术（μParaflo桑格miRBase release 13.0）筛选宫颈鳞癌组织中差异表达的miRNAs。采用茎环RT-PCR方法检测23例临床宫颈癌标本和2株宫颈癌细胞系中miR-375的表达。我们使用pre-miRNA慢病毒载体转染外源性上调SiHa和Caski细胞中的miR-375表达，并使用MTS观察其对紫杉醇敏感性的影响。将稳定过表达miR-375的细胞皮下注射到小鼠体内，以测定肿瘤生长和体内化疗敏感性。其中，miR-375在紫杉醇处理的宫颈细胞和组织中显示出一致的高表达水平。紫杉醇以明显的剂量依赖性方式诱导miR-375表达上调。miR-375在宫颈癌细胞中的强制过表达降低了紫杉醇在体外和体内的敏感性。结论：总的来说，我们的结果表明miR-375可能是紫杉醇耐药宫颈癌的治疗靶点。
Background:Chemo-resistance is one of the key causal factors in cancer death and emerging evidences suggest that microRNAs (miRNAs) have critical roles in the regulation of chemo-sensitivity in cancers. Cervical cancer is one of the most common malignancies in women and insensitive to chemotherapy clinically.Methods:The differentially expressed miRNAs in cervical squamous cell carcinoma tissues were screened by using a microarray platform (μParaflo Sanger miRBase release 13.0). The expression of miR-375 was determined by stem-loop RT–PCR using 23 clinical cervical cancer samples and 2 cervical cancer cell lines. We exogenously upregulated miR-375 expression in SiHa and Caski cells using a pre-miRNA lentiviral vector transfection and observed its impact on paclitaxel sensitivity using MTS. The cells that stably overexpressed miR-375 were subcutaneously injected into mice to determine tumour growth and chemo-sensitivity in vivo.Results:Twenty-one differentially expressed miRNAs were found by miRNA microarray between pro-and post-paclitaxel cervical cancer tissues. Of those, miR-375 showed consistent high expression levels across paclitaxel-treated cervical cells and tissues. Paclitaxel induced upregulated miR-375 expression in a clear dose-dependent manner. Forced overexpression of miR-375 in cervical cancer cells decreased paclitaxel sensitivity in vitro and in vivo.Conclusion:Collectively, our results suggest that miR-375 might be a therapeutic target in paclitaxel-resistant cervical cancer.
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影响因子：
8.4
作者：
Eisenhauer, E. A.;Therasse, P.;Verweij, J.
通讯作者：
Verweij, J.
影响因子：
5.2
作者：
Tanaka, Tetsuji;Toujima, Saori;Tanaka, Junko
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影响因子：
8
作者：
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Sahin, Oe
影响因子：
3.5
作者：
Bamias, Aristotle;Bamia, Christine;Dimopoulos, Meletios-Athanasios
通讯作者：
Dimopoulos, Meletios-Athanasios
影响因子：
8.4
作者：
Guo, Linlang;Liu, Yongguang;Guo, Ying
通讯作者：
Guo, Ying