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.

Download full-text PDF

Source
http://dx.doi.org/10.1002/1873-3468.13615DOI Listing

Publication Analysis

Top Keywords

g1/s checkpoint
12
senescence-apoptosis switch
8
non-small cell
8
cell lung
8
lung cancer
8
boolean model
8
model g1/s
8
checkpoint regulation
8
nsclc cells
8
p21 main
8

Similar Publications

Dual regulation of the levels and function of Start transcriptional repressors drives G1 arrest in response to cell wall stress.

Cell Commun Signal

January 2025

Institut de Biotecnologia i Biomedicina (BIOTECMED) and Departament de Bioquímica i Biologia Molecular, Universitat de València, Burjassot, 46100, Spain.

Background: Many different stress signaling pathways converge in a common response: slowdown or arrest cell cycle in the G1 phase. The G1/S transition (called Start in budding yeast) is a key checkpoint controlled by positive and negative regulators. Among them, Whi7 and Whi5 are transcriptional repressors of the G1/S transcriptional program, yeast functional homologs of the Retinoblastoma family proteins in mammalian cells.

View Article and Find Full Text PDF

Proliferating animal cells maintain a stable size distribution over generations despite fluctuations in cell growth and division size. Previously, we showed that cell size control involves both cell size checkpoints, which delay cell cycle progression in small cells, and size-dependent regulation of mass accumulation rates (Ginzberg et al., 2018).

View Article and Find Full Text PDF

The mechanism of Hespintor (a protein of serpin family) inhibitory action on the growth of inoculated hepatocellular carcinoma was studied in a model of human hepatoma in nude mice by using on long-noncoding RNA (lncRNA) sequencing. Two days after tumor transplantation, Hespintor or normal saline was injected into the caudal vein at a dose of 15 μg/kg (2 times a week over 4 weeks). The tumors were isolated in 4 weeks after subcutaneous injection of human hepatoma MHCC97-H cells.

View Article and Find Full Text PDF

Objectives: Cyclosporine A promotes gingival fibrosis by enhancing the proliferation of gingival fibroblasts, leading to gingival overgrowth. The population of gingival fibroblasts is regulated by cell cycle machinery, which balances cell growth and inhibition. Cells that detect DNA damage pause at the G1/S checkpoint to repair the damage instead of progressing to the S phase.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!