Ask about this productRelated genes to: PCSK2 Blocking Peptide
- Gene:
- PCSK2 NIH gene
- Name:
- proprotein convertase subtilisin/kexin type 2
- Previous symbol:
- NEC2
- Synonyms:
- PC2, SPC2
- Chromosome:
- 20p12.1
- Locus Type:
- gene with protein product
- Date approved:
- 1991-06-07
- Date modifiied:
- 2016-10-05
Related products to: PCSK2 Blocking Peptide
Related articles to: PCSK2 Blocking Peptide
- Human longevity arises from complex genetic and environmental interactions, yet the genetic basis of survival to extreme old age remains underexplored in Asian populations. We performed genome-wide association studies (GWAS) in a Taiwanese cohort, defining survival thresholds at ≥ 85, ≥ 90, and ≥ 95 years, and validated significant loci in an independent cohort. Multiple loci, including ZNF806, NUAK1, TANC1, SLC22A3, PTPRD, and PCSK2, were associated with longevity, of which 14 replicated with consistent effect directions (82% concordance). Allele frequencies aligned with East Asian references but diverged from prior Han Chinese studies, reflecting sub-ethnic variation. Polygenic risk scores (PRSs) alone showed limited predictive ability but provided statistically significant incremental improvement when integrated with clinical covariates. In the external validation cohort, adding PRS modestly improved model discrimination (AUC from 0.900 to 0.904 for ≥ 85 years and from 0.893 to 0.912 for ≥ 90 years) and yielded the largest improvement in the ≥ 95 group (AUC from 0.913 to 0.956; DeLong P < 10⁻⁸), with corresponding gains in reclassification metrics. These findings suggested that while clinical factors remained the primary predictors of survival, genetic risk captured by PRS contributed additional information, particularly at extreme longevity thresholds. Together, the results highlighted an age-dependent genetic architecture enriched for neural, cardio-metabolic, and stress-response pathways and supported the use of genetics-informed models as complementary tools for precision aging research in Taiwanese populations. - Source: PubMed
Publication date: 2026/04/08
Hsieh Ming-ShunYang Shu-MinLiao Shu-HuiGoswami ChayanikaWu Pei-HsuanHsiao Tzu-HungChen Yi-MingHu Sung-YuanHow Chorng-KuangLu Tzu-PinChattopadhyay Amrita - The objective of this study is to investigate the genes associated with lymph node metastasis of Pancreatic adenocarcinoma (PAAD) and their correlation with immune infiltration and ferroptosis. The differentially expressed genes associated with lymphatic metastasis of PAAD were analyzed based on the cancer genome atlas database. The protein-protein interaction network was constructed to screen the hub genes. Functional enrichment analysis was conducted on the hub genes in PAAD with and without lymphoid metastasis. The relationships between the identified genes and both immune cell infiltration and ferroptosis were investigated. LASSO logistic regression analysis was implemented to determine the most relevant genes and construct their risk scores. Multivariate COX regression analysis was conducted based on the genes in the risk score formula. A total of 698 genes were differentially expressed between PAAD with and without lymphatic metastasis, consisting of 153 up-regulated genes and 545 down-Regulated genes. Among the 698 differentially expressed genes, 211 were significantly associated with the overall survival of PAAD patients. The protein-protein interaction network identified 13 hub genes. Only 6 genes, namely CHGA, CHGB, PCSK2, PCSK1N, DLGAP1 and DLGAP3 were down-Regulated in the lymphatic metastasis group. The results of the immune infiltration analysis indicated that the 6 genes were significantly positively correlated with eosinophils, mast cells, pDC, and follicular helper T cells (TFH), and negatively correlated with TH2 cell. Further analysis of the relationship between these 6 genes and ferroptosis revealed that they were positively correlated with the majority of the regulatory factors, namely pyruvate dehydrogenase kinase 4, ALOX15, NCOA4, and BCAT2, and negatively correlated with MGST1 and LCN2. CHGA, PCSK1N, DLGAP1 and DLGAP3 were identified as the 4 most relevant genes through LASSO logistic regression analysis. Multivariate COX regression analysis demonstrated that DLGAP1 was an independent prognostic factor for PAAD. Six hub genes might exert an influence on the initial lymphatic metastasis of PAAD through immune cell infiltration and ferroptosis. - Source: PubMed
Shu QiangLiu XiaoLing - PPP1R1A (protein phosphatase 1 regulatory inhibitor subunit 1A) is a cAMP/PKA-responsive inhibitor of protein phosphatase 1 (PP1) with a pivotal role in pancreatic β-cell physiology. To investigate its functional impact, Ppp1r1a was silenced in INS-1 (832/13) rat β-cells, and proteomic alterations were profiled using label-free DIA mass spectrometry (Orbitrap Exploris 480) with a rat spectral library. Quantitative analysis ( = 4/group) identified ∼2846 proteins with >2-fold change, revealing extensive proteome reprogramming. Key biological processes affected included vesicle trafficking and exocytosis, insulin biosynthesis and processing, organelle organization, mRNA processing, and autophagy. Pathway enrichment highlighted disruptions in insulin secretion, insulin resistance, and mTOR signaling. Crucial β-cell proteins, including INS2, Cacna1a, CPEB2, PCSK2, SNAP25, SYT5, and VAMP7, were significantly downregulated. Validation confirmed reduced phosphorylated AKT levels and p-AKT/T-AKT ratio, consistent with impaired mTOR signaling. Collectively, these findings demonstrate that PPP1R1A is essential for maintaining β-cell function and insulin secretion, and its depletion triggers broad proteomic and signaling alterations. Thus, PPP1R1A emerges as a regulatory node with potential therapeutic relevance in modulating β-cell activity and insulin dynamics in diabetes. - Source: PubMed
Publication date: 2025/12/08
Taneera JalalGiddey Alexander DSoares Nelson CKhalique AnilaMohammed Abdul KhaderMahgoub Mohamed OmerMahgoub Eglal - The role of sphingolipid metabolism (SM) dysregulation in promoting bladder cancer (BLCA) progression and influencing patient prognosis has been well documented. To enhance therapeutic strategies, we aimed to identify key sphingolipid metabolism-related genes (SMGs) and develop a prognostic signature for personalized BLCA management. In this study, 430 BLCA samples from The Cancer Genome Atlas (TCGA) were analyzed via univariate Cox regression to screen critical SMGs involved in tumor progression. A LASSO regression model was applied to minimize overfitting, followed by multivariable Cox regression to construct and validate a SMG-based prognostic signature in an independent cohort. Key findings revealed that SM dysregulation correlated with poor clinical outcomes and eight pivotal prognostic genes (ATP13A2, PCSK2, NR2F1, GSDMB, NFASC, NTF3, LGALS4, and SREBF1) were identified. The resulting risk model demonstrated robust prognostic performance with AUC values of 0.772 (training cohort) and 0.725 (validation cohort). Notably, high-risk patients exhibited a highly active immunological profile characterized by elevated immune scores and enhanced functionality across 26 immune components, including increased infiltration of NK cells, CD8 T cells, and elevated cytolytic activity. These results suggest that SM dysregulation may drive immunomodulatory changes in BLCA microenvironments, offering mechanistic insights into tumor immune evasion. This study provides a novel biomarker tool for risk stratification and highlights SM pathways as potential therapeutic targets for BLCA patients with immune microenvironment dysregulation. - Source: PubMed
Publication date: 2025/11/02
Peng ZechunYang JieJia RuipengWu TianshiZhao Songyun - : Prostate cancer (PC) is among the most common malignancy in men. Several newly diagnosed patients have a locally advanced disease and distant metastasis at the initial diagnosis time. Castration-resistant PC (CRPC) patients have 100% recurrence incidence despite completing a therapeutic regimen, leading to high mortality. Androgen deprivation therapy and androgen inhibitors are initially effective, but resistance is inevitably developed. Epidemiological studies indicated that the Mediterranean diet, with high olive phenolic contents, is associated with a lower incidence of certain malignancies. This study aims at exploring the mCRPC progression and recurrence-suppressive and molecular effects of the major olive leaf phenolic glucoside (-)-oleuropein (OLE). : OLE downregulated the levels of proprotein convertase subtlisin/klexin type 9 (PCSK9) and normalized the low-density lipoprotein receptor (LDLR) in PC cells in vitro. Thus, a PCSK9-LDLR protein-protein interaction (PPI) in silico model was generated and used to assess OLE and its aglycone (OA) ability to bind at PCSK9 and thereby interfere with PCSK9-LDLR PPI. OLE perfectly filled the PCSK9 interface versus OA. Both OLE and OA showed virtual potential to interfere with PCSK9-LDLR PPI. OLE showed modest in vitro viability, migration, and clonogenicity suppressive effects on diverse human PC cell lines. OLE effectively suppressed mCRPC progression and recurrence in a nude mouse xenograft model. RNA-sequencing results proved the , , and downregulation in OLE-treated recurrent tumors versus vehicle control. : Oleuropein is a novel lead useful for the control of mCRPC progression and the prevention of its recurrence via targeting PCSK9 expression and PPI with LDLR. - Source: PubMed
Publication date: 2025/04/25
Ahmed Nehal AMohyeldin Mohamed MEbrahim Hassan YMcGehee Oliver CTarun Md Towhidul IslamEl Sayed Khalid A