A Transcriptional Regulatory Network Model Reveals miR-34a as a Potential Regulator of Proliferation in Cancer Cell Lines
- Resource Type
- Conference
- Authors
- Vargas-Mora, Cristian; Acon, Man Sai; Mora-Rodriguez, Rodrigo; QuirOs, Steve
- Source
- 2018 IEEE International Work Conference on Bioinspired Intelligence (IWOBI) Bioinspired Intelligence (IWOBI), 2018 IEEE International Work Conference on. :1-6 Jul, 2018
- Subject
- Bioengineering
Components, Circuits, Devices and Systems
Computing and Processing
Engineering Profession
General Topics for Engineers
Robotics and Control Systems
Signal Processing and Analysis
Mathematical model
Cancer
Proteins
Inhibitors
Biological system modeling
Tumors
Steady-state
p53
inhibitors
apoptosis
in silico
cancer
MDM4
- Language
The genetic instability caused by the disruption of the mechanism of the DNA-damage response (DDR) has been linked to cancer development. One of the most important and studied mechanism of the DDR is the p53 pathway. This protein acts as a tumor suppressor. MDM2, MDM4 and PLK1 inhibit its proapoptotic activity by binding to its sequence-specific DNA-binding site. To model the interactions between the species with the purpose of finding key points in the regulation of proliferation in cancer cell lines, we propose a transcriptional regulatory network conformed by miRNAs, mARNs and transcription factors involved in the modulation of p53 tumor suppressor protein using Ordinary Differential Equations. Our results suggest miR-34a has a strong control in the regulation of MDM4 and its overexpression results in the decrease of the expression of this protein without significantly affecting the expression of p53. We propose that the combination of miR-34a and small molecule inhibitors of MDM2 may be a therapeutic alternative for treating cancer progression and relapse prevention.