ATM/miR-34a-5p axis regulates a p21-dependent senescence-apoptosis switch in non-small cell lung cancer: a Boolean model of G1/S checkpoint regulation

FEBS Letters

article

Shantanu Gupta¹  Daner A. Silveira¹  José Carlos M. Mombach¹ 

[1] Department of Physics, Universidade Federal de Santa Maria

关键词: ATMmiR-34a-5p axis;    Boolean model;    G1/S checkpoint;    p21;    Senescence-Apoptosis switch;   

DOI  :  10.1002/1873-3468.13615

来源: John Wiley & Sons Ltd.

【 摘 要 】

MicroRNA-34a-5p regulates the G1/S checkpoint in non-small cell lung cancer (NSCLC) cells. Forced expression of miR-34a-5p enhances p21 expression and promotes cellular senescence, whereas knockout of miR-34a-5p decreases senescence and increases apoptosis. This suggests that p21 is the main effector of a senescence-apoptosis switch in NSCLC cells; however, the molecular mechanisms controlling this switch are unclear. In this work, we propose a Boolean model of G1/S checkpoint regulation, contemplating the regulatory influences of p21 by miR-34a-5p. The predicted probabilities of our model are in excellent agreement with experimental data. Our model supports that p21 is the main effector of a senescence/apoptosis switch and that the disruption of the positive feedback involving ATM, miR-34a-5p, and the histone deacetylase HDAC1 abrogates senescence.

【 授权许可】

Unknown