MicroRNA 'signature' during estrogen-mediated mammary carcinogenesis and its reversal by ellagic acid intervention.
MicroRNA 'signature' during estrogen-mediated mammary carcinogenesis and its reversal by ellagic acid intervention.
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DOI：
10.1016/j.canlet.2013.06.012
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发表时间：
2013-10-10
期刊：
影响因子：
9.7
通讯作者：
Gupta, Ramesh C.
中科院分区：
文献类型：
--
作者：
Munagala, Radha;Aqil, Farrukh;Vadhanam, Manicka V.;Gupta, Ramesh C.
miRNA表达失调与包括乳腺癌在内的癌症的发生和进展有关。雌激素（E2）在调节细胞增殖和乳腺癌发生中的作用是众所周知的。最近的报道将几种miRNA与乳腺癌中的雌激素受体联系起来。研究miRNAs的调控作用对于理解E2在人类乳腺癌中的作用以及开发癌症化学预防策略至关重要。在本研究中，我们使用了完善的ACI大鼠模型，E2暴露后发生乳腺肿瘤，并确定了33个显着调制的miRNA在乳腺肿瘤发生过程中的“签名”。这些miRNAs中的几个早在初始E2治疗后3周就发生了改变，并且它们的调节在整个乳腺癌发生过程中持续存在，这表明这些分子变化是早期事件。此外，在我们先前的研究中抑制E2诱导的乳腺肿瘤发生的鞣花酸逆转了E2处理检测到的miR-375、miR-206、miR-182、miR-122、miR- 127和miR-183的失调，并调节其靶蛋白（ERα、细胞周期蛋白D1、RASD 1、FoxO 3a、FoxO 1、细胞周期蛋白G1、Bcl-w和Bcl-2）。这是第一个系统研究早在3周直至肿瘤时间点在ACI大鼠中检查与E2治疗相关的miRNA表达变化的研究。还建立了化学预防剂鞣花酸逆转E2介导的乳腺肿瘤发生过程中调节的miRNA的作用。这些观察结果提供了机制的见解，新的分子事件背后的化学预防作用的鞣花酸和治疗乳腺癌。
Dysregulated miRNA expression has been associated with the development and progression of cancers, including breast cancer. The role of estrogen (E2) in regulation of cell proliferation and breast carcinogenesis is well-known. Recent reports have associated several miRNAs with estrogen receptors in breast cancers. Investigation of the regulatory role of miRNAs is critical for understanding the effect of E2 in human breast cancer, as well as for developing strategies for cancer chemoprevention. In the present study we used the well-established ACI rat model that develops mammary tumors upon E2 exposure and identified a ‘signature’ of 33 significantly modulated miRNAs during the process of mammary tumorigenesis. Several of these miRNAs were altered as early as 3 weeks after initial E2 treatment and their modulation persisted throughout the mammary carcinogenesis process, suggesting that these molecular changes are early events. Furthermore, ellagic acid, which inhibited E2-induced mammary tumorigenesis in our previous study, reversed the dysregulation of miR-375, miR-206, miR-182, miR-122, miR- 127 and miR-183 detected with E2 treatment and modulated their target proteins (ERα, cyclin D1, RASD1, FoxO3a, FoxO1, cyclin G1, Bcl-w and Bcl-2). This is the first systematic study examining the changes in miRNA expression associated with E2 treatment in ACI rats as early as 3 week until tumor time point. The effect of a chemopreventive agent, ellagic acid in reversing miRNAs modulated during E2-mediated mammary tumorigenesis was also established. These observations provide mechanistic insights into the new molecular events behind the chemoprevention action of ellagic acid in and treatment of breast cancer.
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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
天然药物对 microRNA 的调节：化学预防和化疗研究的新兴领域。
影响因子：
3.7
作者：
Li, Yiwei;Kong, Dejuan;Wang, Zhiwei;Sarkar, Fazlul H.
通讯作者：
Sarkar, Fazlul H.
影响因子：
11.2
作者：
Iorio, MV;Ferracin, M;Croce, CM
通讯作者：
Croce, CM
影响因子：
3.8
作者：
Fung, Teresa T.;Schulze, Matthias B.;Hu, Frank B.;Hankinson, Susan E.;Holmes, Michelle D.
通讯作者：
Holmes, Michelle D.
影响因子：
11.2
作者：
Li Y;VandenBoom TG 2nd;Kong D;Wang Z;Ali S;Philip PA;Sarkar FH
通讯作者：
Sarkar FH