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.
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http://dx.doi.org/10.1002/1873-3468.13615 | DOI Listing |
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 PDFJ Ethnopharmacol
January 2025
Department of Veterinary Pathology, School of Veterinary Medicine, Kwame Nkrumah University of Science and Technology (KNUST), Kumasi-Ghana.
Ethnopharmacological Relevance: Ceiba pentandra (L.) Gaertn. (Malvaceae) has been used in Africa traditionally to manage a variety of illnesses, including cancer.
View Article and Find Full Text PDFElife
January 2025
Cell Biology, Hospital for Sick Children, Toronto, Canada.
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 PDFBull Exp Biol Med
December 2024
Department of Laboratory Medicine, Putian University, Putian, China.
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 PDFDiseases
December 2024
Department of Biochemistry and Molecular Biology, Nihon University School of Dentistry at Matsudo, Matsudo 271-8587, Chiba, Japan.
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.
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