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p21/Cyclin E pathway modulates anticlastogenic function of Bmi‐1 in cancer cells
Author(s) -
Deng Wen,
Zhou Yuan,
Tiwari Agnes F.Y.,
Su Hang,
Yang Jie,
Zhu Dandan,
Lau Victoria Ming Yi,
Hau Pok Man,
Yip Yim Ling,
Cheung Annie L.M.,
Guan XinYuan,
Tsao Sai Wah
Publication year - 2014
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.29114
Subject(s) - genome instability , cyclin b , biology , cancer research , cyclin , cyclin a , cyclin d , microbiology and biotechnology , ectopic expression , gene knockdown , cell cycle , cell growth , chromosome instability , cancer , genetics , chromosome , dna damage , gene , dna
Apart from regulating stem cell self‐renewal, embryonic development and proliferation, Bmi‐1 has been recently reported to be critical in the maintenance of genome integrity. In searching for novel mechanisms underlying the anticlastogenic function of Bmi‐1, we observed, for the first time, that Bmi‐1 positively regulates p21 expression. We extended the finding that Bmi‐1 deficiency induced chromosome breaks in multiple cancer cell models. Interestingly, we further demonstrated that knockdown of cyclin E or ectopic overexpression of p21 rescued Bmi‐1 deficiency‐induced chromosome breaks. We therefore conclude that p21/cyclin E pathway is crucial in modulating the anticlastogenic function of Bmi‐1. As it is well established that the overexpression of cyclin E potently induces genome instability and p21 suppresses the function of cyclin E, the novel and important implication from our findings is that Bmi‐1 plays an important role in limiting genomic instability in cylin E‐overexpressing cancer cells by positive regulation of p21.