Prss8

BACKGROUND: Myasthenia gravis (MG) is a chronic autoimmune disorder characterized by fluctuating muscle weakness. Despite the availability of established therapies, the management of MG symptoms remains suboptimal, partially attributed to lack of efficacy or intolerable side-effects. Therefore, new effective drugs are warranted for treatment of MG. METHODS: By employing an analytical framework that combines Mendelian randomization (MR) and colocalization analysis, we estimate the causal effects of blood druggable expression quantitative trait loci (eQTLs) and protein quantitative trait loci (pQTLs) on the susceptibility of MG...

BACKGROUND: Ovarian cancer (OC) is a severe gynecological malignancy with significant diagnostic and therapeutic challenges. The discovery of reliable cancer biomarkers can be used to adjust diagnosis and improve patient care. However, serous OC lacks effective biomarkers. We aimed to identify novel biomarkers for OC and their pathogenic causes. METHODS: The present study used the differentially expressed genes (DEGs) obtained from the "Limma" package and WGCNA modules for intersection analysis to obtain DEGs in OC...

Prostate cancer is a leading cause of cancer-related mortality in males. Dysregulation of RNA Adenine N-6 methylation (m6A) contributes to cancer malignancy. m6A on mRNA may affect mRNA splicing, turnover, transportation and translation. m6A exerts these effects, at least partly, through dedicated m6A reader proteins, including YTHDF2. YTHDF2 is necessary for development while its dysregulation is seen in various cancers including prostate cancer. However, the mechanism underlying the dysregulation and function of YTHDF2 in cancer remains elusive...

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is often treated with FOLFIRINOX, a chemotherapy associated with high toxicity rates and variable efficacy. Therefore, it is crucial to identify patients at risk of early progression during treatment. This study aims to explore the potential of a multi-omics biomarker for predicting early PDAC progression by employing an in-depth mathematical modeling approach. METHODS: Blood samples were collected from 58 PDAC patients undergoing FOLFIRINOX before and after the first cycle...

Pigs are susceptible to cold stress due to the absence of brown fat caused by the partial deletion of uncoupling protein 1 during their evolution. Some local pig breeds in China exhibit potential cold adaptability, but research has primarily focused on fat and intestinal tissues. Skeletal muscle plays a key role in adaptive thermogenesis in mammals, yet the molecular mechanism of cold adaptation in porcine skeletal muscle remains poorly understood. This study investigated the cold adaptability of two pig breeds, Mashen pigs (MS) and Large White pigs (LW), in a four-day cold (4 °C) or normal temperature (25 °C) environment...

The serine proteases CAP1/Prss8 and CAP3/St14 are identified as ENaC channel-activating proteases in vitro, highly suggesting that they are required for proteolytic activation of ENaC in vivo. The present study tested whether CAP3/St14 is relevant for renal proteolytic ENaC activation and affects ENaC-mediated Na+ absorption following Na+ deprivation conditions. CAP3/St14 knockout mice exhibit a significant decrease in CAP1/Prss8 protein expression with altered ENaC subunit and decreased pNCC protein abundances but overall maintain sodium balance...

Prostasin (PRSS8) is a serine protease that metabolizes and moderates the effect of specific substrates. Epidermal growth factor receptor (EGFR), which modulates insulin secretion and pancreatic β-cell proliferation, is regulated via proteolytic shedding by PRSS8. We first detected PRSS8 expression in β-cells of pancreatic islets of mice. To better understand the molecular processes involved in PRSS8-associated insulin secretion, pancreatic β-cell-specific PRSS8 knockout (βKO) and PRSS8-overexpressing (βTG) male mice were generated...

Introduction: We aimed to identify urine biomarkers for screening individuals with adaptability to high-altitude hypoxia with high stamina levels. Although most non-high-altitude natives experience rapid decline in physical ability when ascending to high altitudes, some individuals with high-altitude adaptability continue to maintain high endurance levels. Methods: We divided the study population into two groups: the LC group (low change in endurance from low to high altitude) and HC group (high change in endurance from low to high altitude)...

Ichthyosis is a genetically heterogeneous genodermatosis characterized by severely rough, dry and scaly skin. We report two consanguineous families with congenital ichthyosis. Combined positional mapping and exome sequencing of the two families revealed novel homozygous likely deleterious variants in PRSS8 (encoding prostasin) within a linkage locus on chromosome 16. One variant involved a canonical splice site and was associated with reduced abundance of the normal transcript, while the other was a missense variant that altered a highly conserved residue...

Background: A wide range of disorders can be detected in the urine. Tumor-modifying proteins in the urine may serve as a diagnostic tool for cancer patients and the alterations in their profiles may indicate efficacies of chemotherapy, radiotherapy, and surgery. Methods: We focused on urinary proteomes of patients with prostate cancer and identified tumor-modifying proteins in the samples before and after prostatectomy. Protein array analysis was conducted to evaluate a differential profile of tumor-promoting cytokines, while mass spectrometry-based global proteomics was conducted to identify tumor-suppressing proteins...

Increasing evidences have demonstrated that circular RNA (circRNAs) plays a an essential regulatory role in initiation, progression and immunotherapy resistance of various cancers. However, circRNAs have rarely been studied in bladder cancer (BCa). The purpose of this research is to explore new circRNAs and their potential mechanisms in BCa. A novel ceRNA-regulated network, including 87 differentially expressed circRNAs (DE-circRNAs), 126 DE-miRNAs, and 217 DE-mRNAs was constructed to better understanding the biological processes using Cytoscape 3...

The objective of this study was to evaluate the associations of 92 maternal blood-based proteins with increased infant birth size. The study was performed at the Uppsala University Hospital, Sweden, and included 857 mother and child dyads. The mean age of the women was 30.3 years, and 53.2% were nulliparous. Blood samples were collected at mean 18 + 2 weeks' gestation, and the Olink cardiovascular II panel was used to measure 92 proteins, either known to be or suspected to be markers of cardiovascular and inflammatory disease in humans...

Ovarian cancer is the second most prevalent gynecologic malignancy, and ovarian serous cystadenocarcinoma (OSCA) is the most common and lethal subtype of ovarian cancer. Current screening methods have strong limits on early detection, and the majority of OSCA patients relapse. In this work, we developed and cross-validated a method for detecting gene expression biomarkers able to discriminate OSCA tissues from healthy ovarian tissues and other cancer types with high accuracy. A preliminary ranking-based approach was applied, resulting in a panel of 41 over-expressed genes in OSCA...

The serine protease prostasin (CAP1/Prss8, channel-activating protease-1) is a confirmed in vitro and in vivo activator of the epithelial sodium channel ENaC. To test whether proteolytic activity or CAP1/Prss8 abundance itself are required for ENaC activation in the kidney, we studied animals either hetero- or homozygous mutant at serine 238 (S238A; Prss8cat/+ and Prss8cat/cat ), and renal tubule-specific CAP1/Prss8 knockout (Prss8PaxLC1 ) mice. When exposed to varying Na+ -containing diets, no changes in Na+ and K+ handling and only minor changes in the expression of Na+ and K+ transporting protein were found in both models...

Background: Long noncoding RNAs (lncRNAs) play a significant role in the progression and metastasis of various cancers. LINC00893 has been reported to exert antitumor effect on various cancers such as gastric cancer and thyroid cancer. Bioinformatics analysis also predicted that LINC00893 was downregulated in colon cancer. However, the clinical significance and regulating mechanism of LINC00893 in colon cancer remain unknown. Methods: Expression of LINC00893, miR-146b-3p, and PRSS8 was detected in colon cancer tissues and adjacent nontumor tissues by RT-qPCR, and clinical significance was analyzed by receiver operating characteristic curve...

Experimental nephrotic syndrome leads to activation of the epithelial sodium channel (ENaC) by proteolysis and promotes renal sodium retention. The membrane-anchored serine protease prostasin (CAP1/PRSS8) is expressed in the distal nephron and participates in proteolytic ENaC regulation by serving as a scaffold for other serine proteases. However, it is unknown whether prostasin is also involved in ENaC-mediated sodium retention of experimental nephrotic syndrome. In this study, we used genetically modified knock-in mice with Prss8 mutations abolishing its proteolytic activity (Prss8-S238A) or prostasin activation (Prss8-R44Q) to investigate the development of sodium retention in doxorubicin-induced nephrotic syndrome...

BACKGROUND: Ovarian cancer (OC) is one of the worrisome gynecological cancers worldwide. Given its considerable mortality rate, it is necessary to investigate its oncogenesis. METHODS: In this study, we used systems biology approaches to describe the key gene modules, hub genes, and regulatory drugs associated with serous OC as the novel biomarkers using weighted gene co-expression network analysis (WGCNA). FINDINGS: Our findings have demonstrated that the blue module genes (r = 0...

Intratumoral immune cells were reported to be associated with prognosis of bladder urothelial carcinoma (BUC). However, the role of immune cells related genes in BUC prognosis is less well defined. In the study, we analyzed data retrieved from the Cancer Genome Atlas database and found higher neutrophils and lower T cells infiltration in BUC tumor tissues were significantly correlated with patients' worse prognosis. Additionally, the expression levels of 164 genes were significantly correlated with T cells and neutrophils proportions...

The pathogenesis of ovarian cancer (OC) is complex. Serine Protease 8 (PRSS8) is a potential biomarker for early detection of OC. Multiple databases were used to predict the expression of PRSS8, Sterol regulatory element binding protein (SREBP) and sodium channel epithelial 1alpha subunit (SCNN1A) in OC patients and to detect the relationship among the three. The expressions of PRSS8, SREBF2, SCNN1A and related factors of the pathway were detected by RT-qPCR and Western blot. The cell transfection was used to overexpress or inhibit the expression of PRSS8 and SREBF2, so as to explore its mechanism...

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is the most common type of fatal interstitial lung disease and IPF patients usually have a poor prognosis. Biomarkers that can predict the occurrence, process and prognosis of IPF will be useful for its diagnosis and treatment. This study aimed to identify the potential biomarkers of IPF and analyze the regulation of upstream miRNAs. METHODS: The miRNA and gene expression profiles were downloaded from the Gene Expression Omnibus database...