miR-107 activates ATR/Chk1 pathway and suppress cervical cancer invasion by targeting MCL1.
miR-107 activates ATR/Chk1 pathway and suppress cervical cancer invasion by targeting MCL1.
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DOI：
10.1371/journal.pone.0111860
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Yin J
中科院分区：
文献类型：
--
作者：
Zhou C;Li G;Zhou J;Han N;Liu Z;Yin J
MicroRNAs(MiRNAs)是一类长度约为22个核苷酸的单链非编码RNA。越来越多的证据表明miRNAs可能作为癌基因或肿瘤抑制因子发挥作用。在这里，我们发现miR-107直接靶向MCL1并激活ATR/Chk1途径来抑制宫颈癌细胞的增殖、迁移和侵袭。此外，我们还发现MCL1在宫颈癌中经常上调，MCL1的敲除显著抑制了癌细胞的增殖、迁移和侵袭，而MCL1的异位表达显著增强了这些特性。MCL1表达的恢复可以抵消miR-107对癌细胞的作用。总之，miR-107是一种新的MCL1调节因子，miR-107和MCL1在宫颈癌的发生发展中起重要作用。因此，我们确定了ATR/Chk1途径的一个机制，它涉及miR-107的增加导致MCL1的减少。相应地，我们的结果显示miR-107影响ATR/Chk1信号和基因表达，并提示miR-107是宫颈癌的治疗靶点。我们还证实了紫杉醇通过激活miR-107来抑制宫颈癌细胞的迁移和侵袭，其中miR-107在调节MCL1的表达中起着重要作用。阐明MCL1是由miR-107直接调控的，将极大地加深我们对宫颈癌发病机制的理解，并将为抗癌治疗的发展提供额外的武器。
MicroRNAs (miRNAs) are a class of single-stranded, non-coding RNAs of about 22 nucleotides in length. Increasing evidence implicates miRNAs may function as oncogenes or tumor suppressors. Here we showed that miR-107 directly targeted MCL1 and activated ATR/Chk1 pathway to inhibit proliferation, migration and invasiveness of cervical cancer cells. Moreover, we found that MCL1 was frequently up-regulated in cervical cancer, and knockdown of MCL1 markedly inhibited cancer cell proliferation, migration and invasion, whereas ectopic expression of MCL1 significantly enhances these properties. The restoration of MCL1 expression can counteract the effect of miR-107 on the cancer cells. Together, miR-107 is a new regulator of MCL1, and both miR-107 and MCL1 play important roles in the pathogenesis of cervical cancer. We have therefore identified a mechanism for ATR/Chk1 pathway which involves an increase in miR-107 leading to a decrease in MCL1. Correspondingly, our results revealed that miR-107 affected ATR/Chk1 signalling and gene expression, and implicated miR-107 as a therapeutic target in human cervical cancer. We also demonstrated that taxol attenuated migration and invasion in cervical cancer cells by activating the miR-107, in which miR-107 play an important role in regulating the expression of MCL1. Elucidation of this discovered MCL1 was directly regulated by miR-107 will greatly enhance our understanding of the mechanisms responsible for cervical cancer and will provide an additional arm for the development of anticancer therapies.
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影响因子：
5.4
作者：
Xue, Xiaochang;Cao, Anthony T;Cao, Xiaocang;Yao, Suxia;Carlsen, Eric D;Soong, Lynn;Liu, Chang-Gong;Liu, Xiuping;Liu, Zhanju;Duck, L Wayne;Elson, Charles O;Cong, Yingzi
通讯作者：
Cong, Yingzi
影响因子：
64.8
作者：
Inuzuka, Hiroyuki;Shaik, Shavali;Onoyama, Ichiro;Gao, Daming;Tseng, Alan;Maser, Richard S.;Zhai, Bo;Wan, Lixin;Gutierrez, Alejandro;Lau, Alan W.;Xiao, Yonghong;Christie, Amanda L.;Aster, Jon;Settleman, Jeffrey;Gygi, Steven P.;Kung, Andrew L.;Look, Thomas;Nakayama, Keiichi I.;DePinho, Ronald A.;Wei, Wenyi
通讯作者：
Wei, Wenyi
影响因子：
11.2
作者：
Liu J;Zhou W;Li SS;Sun Z;Lin B;Lang YY;He JY;Cao X;Yan T;Wang L;Lu J;Han YH;Cao Y;Zhang XK;Zeng JZ
通讯作者：
Zeng JZ
miR-23b 作为抑制癌症转移的多效调节剂的全基因组功能筛选
影响因子：
16.6
作者：
Zhang, Hanshuo;Hao, Yang;Xi, Jianzhong Jeff
通讯作者：
Xi, Jianzhong Jeff
DOI：
10.1073/pnas.1104778108
发表时间：
2012-02-21
影响因子：
11.1
作者：
Oakes, Samantha R.;Vaillant, Francois;Lindeman, Geoffrey J.
通讯作者：
Lindeman, Geoffrey J.