A mathematical model of bimodal epigenetic control of miR-193a in ovarian cancer stem cells.
A mathematical model of bimodal epigenetic control of miR-193a in ovarian cancer stem cells.
复制标题
DOI：
10.1371/journal.pone.0116050
复制
发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Chan MW
中科院分区：
文献类型：
--
作者：
Cheng FH;Aguda BD;Tsai JC;Kochańczyk M;Lin JM;Chen GC;Lai HC;Nephew KP;Hwang TW;Chan MW
Accumulating data indicate that cancer stem cells contribute to tumor chemoresistance and their persistence alters clinical outcome. Our previous study has shown that ovarian cancer may be initiated by ovarian cancer initiating cells (OCIC) characterized by surface antigen CD44 and c-KIT (CD117). It has been experimentally demonstrated that a microRNA, namely miR-193a, targets c-KIT mRNA for degradation and could play a crucial role in ovarian cancer development. How miR-193a is regulated is poorly understood and the emerging picture is complex. To unravel this complexity, we propose a mathematical model to explore how estrogen-mediated up-regulation of another target of miR-193a, namely E2F6, can attenuate the function of miR-193a in two ways, one through a competition of E2F6 and c-KIT transcripts for miR-193a, and second by binding of E2F6 protein, in association with a polycomb complex, to the promoter of miR-193a to down-regulate its transcription. Our model predicts that this bimodal control increases the expression of c-KIT and that the second mode of epigenetic regulation is required to generate a switching behavior in c-KIT and E2F6 expressions. Additional analysis of the TCGA ovarian cancer dataset demonstrates that ovarian cancer patients with low expression of EZH2, a polycomb-group family protein, show positive correlation between E2F6 and c-KIT. We conjecture that a simultaneous EZH2 inhibition and anti-estrogen therapy can constitute an effective combined therapeutic strategy against ovarian cancer.
登录
查看更多内容
DOI：
10.1158/1541-7786.mcr-10-0398
发表时间：
2010-12
期刊：
Molecular cancer research : MCR
影响因子：
--
作者：
Li H;Cai Q;Godwin AK;Zhang R
通讯作者：
Zhang R
影响因子：
254.7
作者：
Siegel, Rebecca;Ma, Jiemin;Jemal, Ahmedin
通讯作者：
Jemal, Ahmedin
影响因子：
30.8
作者：
Carroll, Jason S.;Meyer, Clifford A.;Brown, Myles
通讯作者：
Brown, Myles
影响因子：
11.2
作者：
Kozaki, Ken-ichi;Imoto, Issei;Inazawa, Johji
通讯作者：
Inazawa, Johji
CERNA假设：隐藏RNA语言的Rosetta石头？
影响因子：
64.5
作者：
Salmena L;Poliseno L;Tay Y;Kats L;Pandolfi PP
通讯作者：
Pandolfi PP