Seed-mediated RNA interference of androgen signaling and survival networks induces cell death in prostate cancer cells.
Seed-mediated RNA interference of androgen signaling and survival networks induces cell death in prostate cancer cells.
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DOI：
10.1016/j.omtn.2021.03.002
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发表时间：
2021-06-04
期刊：
影响因子：
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通讯作者：
Ruiz-Echevarría MJ
中科院分区：
文献类型：
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作者：
Corbin JM;Georgescu C;Wren JD;Xu C;Asch AS;Ruiz-Echevarría MJ
Resistance to anti-androgen therapy in prostate cancer (PCa) is often driven by genetic and epigenetic aberrations in the androgen receptor (AR) and coregulators that maintain androgen signaling activity. We show that specific small RNAs downregulate expression of multiple essential and androgen receptor-coregulatory genes, leading to potent androgen signaling inhibition and PCa cell death. Expression of different short hairpin/small interfering RNAs (sh-/siRNAs) designed to target TMEFF2 preferentially reduce viability of PCa but not benign cells, and growth of murine xenografts. Surprisingly, this effect is independent of TMEFF2 expression. Transcriptomic and sh/siRNA seed sequence studies indicate that expression of these toxic shRNAs lead to downregulation of androgen receptor-coregulatory and essential genes through mRNA 3′ UTR sequence complementarity to the seed sequence of the toxic shRNAs. These findings reveal a form of the “death induced by survival gene elimination” mechanism in PCa cells that mainly targets AR signaling, and that we have termed androgen network death induced by survival gene elimination (AN-DISE). Our data suggest that AN-DISE may be a novel therapeutic strategy for PCa. Development of effective therapies against advanced prostate cancer (PCa) remains a critical clinical need. We describe a mechanism, AN-DISE, that inhibits the essential androgen receptor signaling pathway, promoting PCa cell death. Through RNA interference of multiple targets simultaneously, AN-DISE could function as a therapeutic approach unlikely to develop resistance.
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影响因子：
16.6
作者：
Ceppi, Paolo;Hadji, Abbas;Kohlhapp, Frederick J.;Pattanayak, Abhinandan;Hau, Annika;Liu, Xia;Liu, Huiping;Murmann, Andrea E.;Peter, Marcus E.
通讯作者：
Peter, Marcus E.
DOI：
10.1056/nejmoa1315815
发表时间：
2014-09-11
期刊：
The New England journal of medicine
影响因子：
--
作者：
Antonarakis ES;Lu C;Wang H;Luber B;Nakazawa M;Roeser JC;Chen Y;Mohammad TA;Chen Y;Fedor HL;Lotan TL;Zheng Q;De Marzo AM;Isaacs JT;Isaacs WB;Nadal R;Paller CJ;Denmeade SR;Carducci MA;Eisenberger MA;Luo J
通讯作者：
Luo J
影响因子：
4.8
作者：
Chen, Xiaofei;Overcash, Ryan;Ruiz-Echevarra, Maria J.
通讯作者：
Ruiz-Echevarra, Maria J.
DOI：
10.1093/database/bav125
发表时间：
2016-02-13
影响因子：
5.8
作者：
DePriest, Adam D.;Fiandalo, Michael V.;Heemers, Hannelore V.
通讯作者：
Heemers, Hannelore V.
影响因子：
64.8
作者：
通讯作者：
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