p16 ink4a

Allele-specific epigenetic events regulate the expression of specific genes such as tumor suppressor genes. Methods to biochemically identify epigenetic regulators remain limited. Here, we used insertional chromatin immunoprecipitation (iChIP) to address this issue. iChIP combined with quantitative mass spectrometry identified DNA methyltransferase 1 (DNMT1) and epigenetic regulators as proteins that potentially interact with a region of the p16INK4A gene that is CpG-methylated in one allele in HCT116 cells...

Breast cancer bone metastases increase fracture risk and are a major cause of morbidity and mortality among women. Upon colonization by tumor cells, the bone microenvironment undergoes profound reprogramming to support cancer progression that disrupts the balance between osteoclasts and osteoblasts, leading to bone lesions. Whether such reprogramming affects matrix-embedded osteocytes remains poorly understood. Here, we demonstrate that osteocytes in breast cancer bone metastasis develop premature senescence and a distinctive senescence-associated secretory phenotype (SASP) that favors bone destruction...

OBJECTIVE: A few studies indicate that human papillomavirus (HPV) induces aberrant expression of microRNAs (miRNAs) and correlate this with p16INK4a in oral dysplasia (OD) and oral squamous cell carcinoma (OSCC). Therefore, this study aimed to evaluate the expression of miRNA-21, miRNA-22, and miRNA-224 by q-PCR and the p16 INK4a by immunohistochemical (IHC) as markers for HPV-positive OSCC and OD in comparison to controls as miRNA expression can be altered by the HPV oncogenes and hence can be used as a biomarker for HPV positive cases...

Activating point mutations in codons 12, 13, and 61 of the KRAS gene and loss of p16 expression, a tumor suppressor gene, are common genetic alterations in periampullary cancer (PAC). The present study explores expression profile of KRAS and p16 genes in PAC and its prognostic relevance. A total of 50 patients with PAC who underwent potentially curative pancreaticoduodenectomy were included in the study. Formalin-fixed, paraffin-embedded tissue samples were analyzed for point mutations in codons 12 and 13 of KRAS and codon 9 of p16 using polymerase chain reaction...

BACKGROUND: The association of Human Papilloma Virus (HPV) and Human Syncytial Virus (HSV) infection with inflammatory and potentially malignant disorders of the oral cavity (OPMD) is unknown. The aim of this cross-sectional study was to stablish the expression of the p16INK4A and HSV proteins, to test potential correlation between those parameters in biopsies from clinically diagnosed oral lesions. METHODS: Immunochemical analysis of 211 formalin-fixed, paraffin-embedded (FFPE) blocks from 211 individuals was provided...

Age-dependent accumulation of amyloid plaques in patients with sporadic Alzheimer's disease (AD) is associated with reduced amyloid clearance. Older microglia have a reduced ability to phagocytose amyloid, so phagocytosis of amyloid plaques by microglia could be regulated to prevent amyloid accumulation. Furthermore, considering the aging-related disruption of cell cycle machinery in old microglia, we hypothesize that regulating their cell cycle could rejuvenate them and enhance their ability to promote more efficient amyloid clearance...

NIPP1 is a ubiquitously expressed regulatory subunit of protein phosphatase-1. Its embryonic deletion in keratinocytes causes chronic sterile skin inflammation, epidermal hyperproliferation and resistance to mutagens in adult mice. To explore the primary effects of NIPP1 deletion, we first examined hair-cycle progression of NIPP1 skin knockouts (SKOs). The entry of the 1st hair cycle in the SKOs was delayed due to prolonged quiescence of hair-follicle stem cells (HFSCs). In contrast, the entry of the 2nd hair cycle in the SKOs was advanced as a result of precocious activation of HFSCs...

Cellular senescence is a major driver of aging and disease. Here we show that substrate stiffness modulates the emergence and magnitude of senescence phenotypes post induction. Using a primary dermal fibroblast model of senescence, we show that decreased substrate stiffness accelerates cell-cycle arrest during senescence development and regulate expression of conventional protein-based biomarkers of senescence. We found that the expression of these senescence biomarkers, namely p21 WAF1/CIP1 ( CDKN1a ) and p16 INK4a ( CDKN2a ) are mechanosensitive and are in-part regulated by myosin contractility through focal adhesion kinase (FAK)-ROCK signaling...

Numerous studies have demonstrated that regulatory T (Treg) cells play an important role in the tumour microenvironment (TME). The aim of this study was to investigate whether VEGFR2 affects the expression of miR-3200-3p in exosomes secreted by tumour cells, thereby influencing Treg senescence in the TME. The results showed that VEGFR2 expression level was the highest in Calu-1 cells, and after transfection with si-VEGFR2, the exosomes secreted from Calu-1 cells were extracted and characterised with no significant difference from the exosomes of the untransfected group, but the expression of miR-3200-3p in the exosomes of the transfected si-VEGFR2 group was elevated...

UNLABELLED: The recent WHO classification of female genital tracts recommends cervical carcinomas to be further subtyped as HPV-associated and HPV-independent and accepted p16 immunoreactivity as a surrogate biomarker for HPV testing. This paper presents the clinicopathological spectrum of cervical carcinomas in correlation with p16 immunoreactivity. AIMS AND OBJECTIVES: This study aims to evaluate the immunoreactivity of p16 in cervical carcinoma, subtype them into HPV-associated and HPV-independent based on p16 immunoreactivity, and correlate them with clinicopathological features...

Contrast-induced acute kidney injury (CI-AKI) is the third leading cause of hospital-acquired acute kidney injury. Cellular senescence is associated with CI-AKI. P16INK4a (p16) is a cell cycle regulator and link to aging and senescence. We found that the expression of p16 was elevated in CI-AKI renal tissues, however its role in CI-AKI remains insufficiently understood. In this study, we used p16 knockout (p16KO) mice and wild-type (WT) littermates to establish CI-AKI mice model to elucidate the impact of p16 on CI-AKI...

BACKGROUND: Intervertebral disc degeneration (IDD) is a leading contributor to low back pain (LBP). Autophagy, strongly activated by hypoxia and nutrient starvation, is a vital intracellular quality control process that removes damaged proteins and organelles to recycle them for cellular biosynthesis and energy production. While well-established as a major driver of many age-related diseases, autophagy dysregulation or deficiency has yet been confirmed to cause IDD. METHODS: In vitro, rat nucleus pulposus (NP) cells treated with bafilomycin A1 to inhibit autophagy were assessed for glycosaminoglycan (GAG) content, proteoglycan synthesis, and cell viability...

Glaucoma, a prevalent cause of permanent visual impairment worldwide, is characterized by the progressive degeneration of retinal ganglion cells (RGCs). NADPH oxidase (NOX) 1 and NOX4 are pivotal nodes in various retinal diseases. Setanaxib, a potent and highly selective inhibitor of NOX1 and NOX4, can impede the progression of various diseases. This study investigated the efficacy of setanaxib in ameliorating retinal ischemia-reperfusion (I/R) injury and elucidated its underlying mechanisms. The model of retinal I/R induced by acute intraocular hypertension and the oxygen-glucose deprivation/reoxygenation (OGD/R) model of primary RGCs were established...

Senescent cells drive age-related tissue dysfunction via the induction of a chronic senescence-associated secretory phenotype (SASP). The cyclin-dependent kinase inhibitors p21 Cip1 and p16 Ink4a have long served as markers of cellular senescence. However, their individual roles remain incompletely elucidated. Thus, we conducted a comprehensive examination of multiple single-cell RNA sequencing (scRNA-seq) datasets spanning both murine and human tissues during aging. Our analysis revealed that p21 Cip1 and p16 Ink4a transcripts demonstrate significant heterogeneity across distinct cell types and tissues, frequently exhibiting a lack of co-expression...

Osteoarthritis (OA) is a degenerative joint disease and a leading cause of disability worldwide. Aging is a major risk factor for OA, but the specific mechanisms underlying this connection remain unclear. Although chondrocytes rarely divide in adult articular cartilage, they undergo replicative senescence in vitro which provides an opportunity to study changes related to aging under controlled laboratory conditions. In this pilot study, we performed bulk RNA sequencing on early- and late-passage human articular chondrocytes to identify transcriptomic changes associated with cellular aging...

Brain white matter tracts undergo structural and functional changes linked to late-life cognitive decline, but the cellular and molecular contributions to their selective vulnerability are not well defined. In naturally aged mice, we demonstrate that senescent and disease-associated microglia (DAM) phenotypes converge in hippocampus-adjacent white matter. Through gold-standard gene expression and immunolabeling combined with high-dimensional spatial mapping, we identified microglial cell fates in aged white matter characterized by aberrant morphology, microenvironment reorganization, and expression of senescence and DAM markers, including galectin 3 (GAL3/Lgals3), B-cell lymphoma 2 (Bcl2), and cyclin dependent kinase inhibitors, including Cdkn2a/p16 ink4a ...

Arsenic exposure is a public health concern worldwide. Skin damage, as a typical lesion of arsenic exposure, the mechanism is still unknown. Studies have found that cellular senescence plays a key role in arsenic-induced skin damage, and the previous research found that the ERK/CEBPB signaling pathway may be an important molecular event of arsenic-induced skin cell senescence, but its specific mechanism is unknown. In this study, genetic engineering technology was used to construct stable HaCaT cell lines, and the role and mechanism of ERK/CEBPB signaling pathway in arsenic-induced HaCaT cell senescence were verified by knockdown and overexpression of ERK and CEBPB in both forward and backward...

OBJECTIVES: Despite treatment, one-third of patients with lupus nephritis (LN) show a decline in renal function. Prognostic markers of poor outcome as well as novel therapeutic targets are therefore highly sought. We showed that p16INK4a , a marker of cellular senescence, is observed in baseline kidney biopsies from patients with LN, and is associated with renal disease. Here, we set out to assess for whether these findings are recapitulated in the B6. NZMSle1/Sle2/Sle3 (B6. Sle1.2.3 ) mouse model of spontaneous lupus...

We intended to update human papillomavirus (HPV) prevalence and p16INK4a positivity in oropharyngeal squamous cell carcinomars (SCC), and calculate HPV attributable fraction (AF) for oropharyngeal SCC by geographic region. We searched Medline, Embase, and the Cochrane Library to identify published studies of HPV prevalence and p16INK4a positivity alone or together in oropharyngeal SCC before December 28, 2021. Studies that reported type-specific HPV DNA prevalence using broad-spectrum PCR-based testing methods were included...

More specific screening systems for cervical cancer may become necessary as the human papillomavirus (HPV) vaccine becomes more widespread. Although p16/Ki-67 dual-staining cytology has several advantages, it requires advanced diagnostic skills. Here, we developed an automated on-chip immunostaining method using a microfluidic device. An electroactive microwell array (EMA) microfluidic device with patterned thin-film electrodes at the bottom of each microwell was used for single-cell capture by dielectrophoresis...