This study was to explore the association between gene variants and p21 expression and investigate the TP53-independent p21 regulation in hepatitis B virus (HBV) related hepatocellular carcinoma (HCC) patients from Guangxi by genome-wide association study. 426 HBV-related HCC patients were enrolled. Results showed that, after quality control, a total of 21,643 SNPs were identified in 107 p21 positive and 298 p21 negative patients. The variants of epidermal growth factor receptor (EGFR; rs2227983 and rs6950826) and spectrin repeat containing, nuclear envelope 2 (SYNE2; rs8010699, rs4027405 and rs1890908) were associated with p21 expression. Moreover the haplotype block (rs2227983 and rs6950826, r(2) = 0.378) in EGFR and the haplotype block in SYNE2 (rs8010699 was in strong LD with rs4027405 and rs1890908 (r(2) = 0.91 and 0.70, respectively)) were identified, and the haplotype A-G of EGFR and haplotype G-A-A of SYNE2 were significantly associated with p21 expression (P < 0.01). rs4027405 and rs1890908 were significantly associated with overall survival, and patients with AG/GG genotypes of SYNE2 gene had a worse overall survival (P = 0.001, P = 0.002). Our findings indicate that variants of EGFR and SYNE2 play an important role in p21 regulation and are associated with the clinical outcome of HBV-related HCC in a TP53-indenpdent manner.
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http://dx.doi.org/10.1038/srep31237 | DOI Listing |
FEBS J
January 2025
Université d'Angers, Inserm, CNRS, CRCI2NA, ICO, Angers, France.
Senescence is a tumor suppressor mechanism triggered by oncogene expression and chemotherapy treatment. It orchestrates a definitive cessation of cell proliferation through the activation of the p53-p21 and p16-Rb pathways, coupled with the compaction of proliferative genes within heterochromatin regions. Some cancer cells have the ability to elude this proliferative arrest but the signaling pathways involved in circumventing senescence remain to be characterized.
View Article and Find Full Text PDFTissue Cell
December 2024
Department of Gastrointestinal Surgery, Yantaishan Hospital, Yantai, Shandong Province, China. Electronic address:
Histocompatibility minor 13 (HM13) is a signal sequence stubbed intramembrane cleavage catalytic protein. Increasing evidence supports the association among HM13 expression, tumor-infiltrating immune cells (TIICs), and cancer. However, its role on formation and progression of colorectal cancer (CRC) has not been explored.
View Article and Find Full Text PDFCell Death Dis
January 2025
Amsterdam UMC location Vrije Universiteit Amsterdam, Department of Molecular Cell Biology and Immunology, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.
Aging of the brain vasculature plays a key role in the development of neurovascular and neurodegenerative diseases, thereby contributing to cognitive impairment. Among other factors, DNA damage strongly promotes cellular aging, however, the role of genomic instability in brain endothelial cells (EC) and its potential effect on brain homeostasis is still largely unclear. We here investigated how endothelial aging impacts blood-brain barrier (BBB) function by using excision repair cross complementation group 1 (ERCC1)-deficient human brain ECs and an EC-specific Ercc1 knock out (EC-KO) mouse model.
View Article and Find Full Text PDFSci Rep
January 2025
Department of General Surgery, XiangYa Hospital Central South University, No. 87 XiangYa Road, Changsha, 410008, Hunan, China.
Papillary thyroid cancer (PTC) is often characterized by indolent behavior, small tumors with slow cell proliferation and a tendency to metastasize to cervical lymph node simultaneously, and the molecular mechanisms underlying that remain poorly understood. In this study, FN1 was the hottest gene of PTC and distinctive expression in PTC cells. FN1 deficiency severely inhibited the p53 signaling pathway, especially cyclin proteins, resulting in increased cell growth but hampered invasion.
View Article and Find Full Text PDFNat Commun
January 2025
Laboratory for Experimental Oncology and Radiobiology, Center for Experimental and Molecular Medicine, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.
Colorectal cancer (CRC) is stratified into four consensus molecular subtypes (CMS1-4). CMS3 represents the metabolic subtype, but its wiring remains largely undefined. To identify the underlying tumorigenesis of CMS3, organoids derived from 16 genetically engineered mouse models are analyzed.
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