Circulating MiR-125b as a marker predicting chemoresistance in breast cancer.
Circulating MiR-125b as a marker predicting chemoresistance in breast cancer.
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循环 MiR-125b 作为预测乳腺癌化疗耐药性的标志物
DOI：
10.1371/journal.pone.0034210
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Luo H
中科院分区：
文献类型：
--
作者：
Wang H;Tan G;Dong L;Cheng L;Li K;Wang Z;Luo H
化疗是乳腺癌治疗模式中的一个重要组成部分。然而，癌细胞对化疗药物的耐药性往往会导致随后的复发和转移。因此，鉴定分子标志物以预测治疗结果是必要的。本研究的目的是评估循环microRNAs(MiRNAs)的表达是否可以预测接受辅助化疗的乳腺癌患者的临床预后。采用实时荧光定量聚合酶链式反应技术检测56例乳腺癌浸润性导管癌患者治疗前血清中miRNAs的含量。分别采用增殖细胞核抗原(PCNA)免疫组织化学染色和原位末端标记法(TUNEL)检测化疗对肿瘤细胞增殖和凋亡的影响。在检测的miRNA中，只有miR-125b与治疗反应显著相关，在无反应的患者中表达水平较高(n = 26，46%；p = 0.008)。此外，miR-125b高表达的乳腺癌在新辅助化疗后获得的相应手术标本中，增殖细胞比例较高，而凋亡细胞比例较低。在体外观察到异位表达miR-125b的乳腺癌细胞对抗癌药物的耐药性增加；相反，降低miR-125b的水平使乳腺癌细胞对化疗敏感。此外，我们还证明了E2F3是miR-125b在乳腺癌细胞中的直接靶点。这些数据表明，循环中miR-125b的表达与乳腺癌的化疗耐药有关。这一发现对在新的抗癌策略中克服化疗耐药性的靶向治疗的开发具有重要意义。
Chemotherapy is an important component in the treatment paradigm for breast cancers. However, the resistance of cancer cells to chemotherapeutic agents frequently results in the subsequent recurrence and metastasis. Identification of molecular markers to predict treatment outcome is therefore warranted. The aim of the present study was to evaluate whether expression of circulating microRNAs (miRNAs) can predict clinical outcome in breast cancer patients treated with adjuvant chemotherapy. Circulating miRNAs in blood serum prior to treatment were determined by quantitative Real-Time PCR in 56 breast cancer patients with invasive ductal carcinoma and pre-operative neoadjuvant chemotherapy. Proliferating cell nuclear antigen (PCNA) immunostaining and TUNEL were performed in surgical samples to determine the effects of chemotherapy on cancer cell proliferation and apoptosis, respectively. Among the miRNAs tested, only miR-125b was significantly associated with therapeutic response, exhibiting higher expression level in non-responsive patients (n = 26, 46%; p = 0.008). In addition, breast cancers with high miR-125b expression had higher percentage of proliferating cells and lower percentage of apoptotic cells in the corresponding surgical specimens obtained after neoadjuvant chemotherapy. Increased resistance to anticancer drug was observed in vitro in breast cancer cells with ectopic miR-125b expression; conversely, reducing miR-125b level sensitized breast cancer cells to chemotherapy. Moreover, we demonstrated that the E2F3 was a direct target of miR-125b in breast cancer cells. These data suggest that circulating miR-125b expression is associated with chemotherapeutic resistance of breast cancer. This finding has important implications in the development of targeted therapeutics for overcoming chemotherapeutic resistance in novel anti-cancer strategies.
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影响因子：
254.7
作者：
Jemal, Ahmedin;Siegel, Rebecca;Thun, Michael J.
通讯作者：
Thun, Michael J.
影响因子：
3.9
作者：
Lange CA;Yee D
通讯作者：
Yee D
DOI：
10.1186/bcr2839
发表时间：
2011-03-04
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Hannafon BN;Sebastiani P;de las Morenas A;Lu J;Rosenberg CL
通讯作者：
Rosenberg CL
影响因子：
3.8
作者：
He, Min;Guo, Qulian;Hu, Guoqing
通讯作者：
Hu, Guoqing
影响因子：
7.5
作者：
Iaquinta, Phillip J.;Lees, Jacqueline A.
通讯作者：
Lees, Jacqueline A.