Frontiers in Molecular Biosciences最新文献

{"title":"Homologous recombination deficiency test validation in patients with high-grade advanced ovarian cancer.","authors":"Angelica Nogueira Rodrigues, Andreza Karine de Barros Almeida Souto, Diocésio Alves Pinto de Andrade, Larissa Müller Gomes, Sandra Satie Koide, Renata de Godoy E Silva, Bruno Batista de Souza, Juliana Doblas Massaro, Andréia Cristina de Melo, Andrea Morais Borges, Camila Giro, Carlos Augusto Vasconcelos de Andrade, Cesar Martins da Costa, Daniel Luiz Gimenes, Eduardo Caminha Bandeira de Mello, Fernanda Cesar de Oliveira, Frederico Müller de Toledo Lima, Gabriel Lima Lopes, Gustavo de Oliveira Bretas, Gustavo Guerra Jacob, Herika Lucia da Costa Silva, Juliana Ferrari Notaro, Lara Ladislau Alves, Marcos Veloso Moitinho, Mirian Cristina da Silva, Roberto Abramoff, Thais Amaral da Cunha Rauber, Rodrigo Dienstmann, Fernanda Christtanini Koyama","doi":"10.3389/fmolb.2025.1524594","DOIUrl":"10.3389/fmolb.2025.1524594","url":null,"abstract":"<p><strong>Background: </strong>Along with <i>BRCA</i> mutation status, homologous recombination deficiency (HRD) testing is a prognostic and predictive biomarker for poly-ADP-ribose polymerase (PARP) inhibitor therapy indication in high-grade epithelial ovarian, fallopian tube, or peritoneal cancer. Approximately 50% of high-grade serous ovarian cancers exhibit HRD, even in the absence of germline or somatic <i>BRCA</i>1/2 loss-of-function mutations. In this scenario, access to a validated diagnostic HRD test can optimize treatment selection and increase the effectiveness of the intervention.</p><p><strong>Objective: </strong>To technically validate an <i>in-house</i> next-generation sequencing (NGS)-based HRD test, QIAseq Custom Panel (QIAGEN), by comparing it with the reference assay, MyChoice CDx® Plus HRD (Myriad Genetics), which is used in routine care.</p><p><strong>Methods: </strong>This is a prospective cohort study conducted at the Oncoclínicas Precision Medicine (OCPM) laboratory using samples from patients with advanced or relapsed platinum-sensitive ovarian cancer eligible for HRD testing in a diagnostic clinical setting at Oncoclínicas and Co. We assessed the performance of the in-house test (GS Focus HRD) using Cohen's kappa statistic to measure agreement with the gold standard assay (MyChoice® HRD Plus CDx) in HRD status classification, along with other accuracy metrics.</p><p><strong>Results: </strong>In total, 41 samples were analyzed (20 HRD-positive, 19 HRD-negative, and 2 inconclusive results with the MyChoice® HRD Plus CDx assay). The GS Focus HRD test demonstrated high concordance for HRD status with the reference test (kappa: 0.8 and 95% CI: 0.60-0.98). Overall accuracy, sensitivity, and specificity were 90%. Six samples had <i>BRCA1</i>/<i>2</i> mutations identified by the MyChoice® HRD Plus CDx, all of which were detected by the GS Focus HRD test.</p><p><strong>Conclusion: </strong>In summary, the results demonstrate substantial agreement and high accuracy of the NGS-based GS Focus HRD test compared to MyChoice® HRD Plus CDx. Our in-house assay is eligible for diagnostic test approval and market access as per Brazilian regulations.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1524594"},"PeriodicalIF":3.9,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11850238/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143499020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: The emerging role of protein methylation/demethylation modification in disease and homeostasis.","authors":"Yan-Jun Liu, Jian-Fei Lu, Xin Peng, Guan-Jun Yang","doi":"10.3389/fmolb.2025.1565598","DOIUrl":"10.3389/fmolb.2025.1565598","url":null,"abstract":"","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1565598"},"PeriodicalIF":3.9,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11847662/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143491527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Distinct roles of Constitutive Photomorphogenesis Protein 1 homolog (COP1) in human hepatocyte models.","authors":"Sébastien Soubeyrand, Paulina Lau, Ruth McPherson","doi":"10.3389/fmolb.2025.1548582","DOIUrl":"10.3389/fmolb.2025.1548582","url":null,"abstract":"<p><strong>Introduction: </strong>Constitutive Photomorphogenesis Protein 1 homolog (COP1) is a conserved E3 ligase with key roles in several biological systems. Prior work in hepatocyte-derived tumors categorized COP1 as an oncogene, but its role in untransformed hepatocytes remains largely unexplored. Here, we have investigated the role of COP1 in primary human hepatocytes and two transformed hepatocyte models, HepG2 and HuH-7 cells.</p><p><strong>Methods: </strong>The role of COP1 was tested by silencing and transduction experiments in HepG2, HuH-7, and primary human hepatocytes. Transcription array data of COP1-suppressed cells were generated and analyzed using clustering analyses. Cellular impacts were examined by proliferation assays, qRT-PCR, western blotting, reporter assays, and APOB enzyme-linked immunosorbent assays.</p><p><strong>Results and discussion: </strong>COP1 suppression had no noticeable impact on HepG2 and HuH-7 proliferation and was associated with contrasting rather than congruent transcriptome changes. Transcriptomic changes were consistent with perturbed metabolism in primary hepatocytes and HepG2 cells and impaired cell cycle regulation in HuH-7 cells. In HepG2 and primary hepatocytes but not in HuH-7 cells, COP1 suppression reduced the expression of important hepatic regulators and markers. COP1 downregulation reduced hepatic nuclear factor-4 alpha (HNF4A) abundance and function, as assessed by a lower abundance of key HNF4A targets, reduced APOB secretion, and reporter assays. HNF4A function could be restored by introducing a siRNA-resistant COP1 transgene, whereas HNF4A restoration partially rescued COP1 silencing in HepG2 cells. Our results identify and detail a pivotal regulatory role of COP1 in hepatocytes, in part through HNF4A.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1548582"},"PeriodicalIF":3.9,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11842253/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Defining the high-risk category of patients with cutaneous melanoma: a practical tool based on prognostic modeling.","authors":"Oleksandr Dudin, Ozar Mintser, Vitalii Gurianov, Nazarii Kobyliak, Denys Kozakov, Sofiia Livshun, Oksana Sulaieva","doi":"10.3389/fmolb.2025.1543148","DOIUrl":"10.3389/fmolb.2025.1543148","url":null,"abstract":"<p><strong>Introduction: </strong>Although most cutaneous melanoma (CM) in its early stages is treatable, the risk of recurrence remains high and there is a particular ambiguity on patients prognosis. This drives to identification of prognostic biomarkers for predicting CM recurrence to guide appropriate treatment in patients with localized melanoma.</p><p><strong>Aim: </strong>This study aimed to develop a prognostic model for assessing the risk of recurrence in patients with CM, enabling prompt prognosis-driven further clinical decision-making for high-risk patients.</p><p><strong>Materials and methods: </strong>This case-control study included 172 patients with CM recurrence (high-risk group) and 30 patients with stable remission (low-risk group) 3 years after primary diagnosis. The impact of sex, age at diagnosis, anatomical site, histological characteristics (the histological type, pathological stage, ulceration; the depth of invasion, mitotic rate, lymphovascular invasion, neurotropism, association with a nevus, tumor-infiltrating lymphocyte density, tumor regression and <i>BRAF</i> codon 600 mutation status) on CM recurrence was evaluated.</p><p><strong>Results: </strong>Five independent variables, including nodal status, a high mitotic rate, Breslow thickness, lymphovascular invasion, perineural invasion and regression features were identified as the most significant. A 5-factor logistic regression model was developed to assess the risk of melanoma recurrence. The sensitivity and specificity of the model were 86.1% and 72.7%, respectively.</p><p><strong>Conclusion: </strong>The developed model, which relies on routine histological features, allows the identification of individuals at high risk of CM recurrence to tailor their further management.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1543148"},"PeriodicalIF":3.9,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11842245/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum glutathione peroxidase-3 concentration at diagnosis as a biomarker for assessing disease activity and damage of antineutrophil cytoplasmic antibody-associated vasculitis at diagnosis.","authors":"Jihye Chung, Jang Woo Ha, Yong-Beom Park, Sang-Won Lee","doi":"10.3389/fmolb.2025.1549454","DOIUrl":"10.3389/fmolb.2025.1549454","url":null,"abstract":"<p><strong>Background: </strong>In this study, we investigated whether serum glutathione peroxidase-1 (GPX-3) concentration at diagnosis could be used to assess vasculitis activity and damage at diagnosis in immunosuppressive drug-naïve patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV).</p><p><strong>Methods: </strong>We included 71 immunosuppressive drug-naïve patients newly diagnosed with AAV. Medical records were retrospectively reviewed and serum GPX-3 concentration was measured using serum samples collected and stored at diagnosis. The degree of vascular activity and extent of damage were assessed using the Birmingham vasculitis activity score (BVAS) and vasculitis damage index (VDI), respectively. Poor outcomes including all-cause mortality, end-stage kidney disease, and cerebrovascular and cardiovascular diseases were also investigated.</p><p><strong>Results: </strong>The median age of the study subjects was 63.0 years, 26 and 45 patients were males and females, respectively. The median GPX-3 concentration was measured as 82.8 ng/mL. Serum GPX-3 concentration at diagnosis was inversely correlated with BVAS (r = -0.280), VDI (r = -0.263), and C-reactive protein (r = -0.261) at diagnosis, whereas, it was positively correlated with haemoglobin (r = 0.255), and serum albumin (r = 0.240) at diagnosis, respectively. However, serum GPX-3 concentration at diagnosis was not significantly associated with poor outcomes during follow-up in patients with AAV.</p><p><strong>Conclusion: </strong>In this study, we demonstrated for the first time that serum GPX-3 concentration at diagnosis correlates with vasculitis activity and damage at diagnosis in patients with AAV, suggesting a possible role of serum GPX-3 as a complementary biomarker for assessing AAV activity in real clinical practice.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1549454"},"PeriodicalIF":3.9,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11842223/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Construction of a circadian rhythm-related gene signature for predicting the prognosis and immune infiltration of breast cancer.","authors":"Lin Ni, He Li, Yanqi Cui, Wanqiu Xiong, Shuming Chen, Hancong Huang, Zhiwei Wang, Hu Zhao, Bing Wang","doi":"10.3389/fmolb.2025.1540672","DOIUrl":"10.3389/fmolb.2025.1540672","url":null,"abstract":"<p><strong>Objectives: </strong>In this study, we constructed a model based on circadian rhythm associated genes (CRRGs) to predict prognosis and immune infiltration in patients with breast cancer (BC).</p><p><strong>Materials and methods: </strong>By using TCGA and CGDB databases, we conducted a comprehensive analysis of circadian rhythm gene expression and clinicopathological data. Three different machine learning algorithms were used to screen out the characteristic circadian genes associated with BC prognosis. On this basis, a circadian gene prediction model about BC prognosis was constructed and validated. We also evaluated the association of the model's risk score with immune cells and immune checkpoint genes, and analyzed prognostic genes and drug sensitivity in this model.</p><p><strong>Results: </strong>We screened 62 DEGs, including 30 upregulated genes and 32 downregulated genes, and performed GO and KEGG analysis on them. The above 62 DEGs were included in Cox analysis, LASSO regression, Random Forest and SVMV-RFE, respectively, and then the intersection was used to obtain 5 prognostic related characteristic genes (SUV39H2, OPN4, RORB, FBXL6 and SIAH2). The Risk Score of each sample was calculated according to the expression level and risk coefficient of 5 genes, Risk Score= (SUV39H2 expression level ×0.0436) + (OPN4 expression level ×1.4270) + (RORB expression level ×0.1917) + (FBXL6 expression level ×0.3190) + (SIAH2 expression level × -0.1984).</p><p><strong>Conclusion: </strong>SUV39H2, OPN4, RORB and FBXL6 were positively correlated with Risk Score, while SIAH2 was negatively correlated with Risk Score. The above five circadian rhythm genes can construct a risk model for predicting the prognosis and immune invasion of BC.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1540672"},"PeriodicalIF":3.9,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11839441/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143467567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deciphering the role of miRNA-mRNA interactions in cerebral vasospasm post intracranial hemorrhage.","authors":"Xiang Chu, Xiyan Zhu, Honghao Xu, Wenbing Zhao, Debin Guo, Xing Chen, Jinze Wu, Lei Li, Hao Wang, Jun Fei","doi":"10.3389/fmolb.2025.1492729","DOIUrl":"10.3389/fmolb.2025.1492729","url":null,"abstract":"<p><p>Cerebral vasospasm (CVS), a serious complication following subarachnoid hemorrhage, is associated with high rates of mortality and disability. Emerging evidence suggests that abnormal miRNA and mRNA are involved in the development of CVS. This study aims to identify essential miRNA-mRNA regulatory pairs that contribute to CVS pathogenesis. We compared the differences between spasm and non-spasm groups after cerebral hemorrhage, identifying 183 differentially expressed genes (DEGs) and 19 differentially expressed miRNAs (DEMs) related to cerebral vasospasm from the GEO database. Further functional enrichment and KEGG analysis revealed that these DEGs were enriched in several terms and pathways, including the PI3K/AKT/mTOR signaling pathway, oxidative phosphorylation pathway, RNA degradation, and folate biosynthesis signaling pathway. By employing the degree scores method for each gene, we identified the top 10 genes and developed a protein-protein interaction (PPI) network. Additionally, we discovered 19 DEMs associated with CVS and integrated them with mRNA dataset analysis to construct a miRNA-mRNA network, which comprised 8 functionally differentially expressed DEMs and 6 target mRNAs. Experimental validation confirmed the significant regulatory roles of four miRNAs (Let-7a-5p, miR-24-3p, miR-29-3p, and miR-132-3p) and two mRNAs (CDK6 and SLC2A1) in the pathogenesis of CVS. In conclusion, this comprehensive study identifies pivotal miRNAs and their target mRNAs associated with CVS through an integrated bioinformatics analysis of miRNA-mRNA co-expression networks. This approach elucidates the intricate molecular mechanisms underlying CVS and uncovers potential therapeutic targets, thereby providing a valuable foundation for refining and optimizing future treatment strategies.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1492729"},"PeriodicalIF":3.9,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11840915/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143467622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The diagnostic and prognostic significance of HOXC13-AS and its molecular regulatory mechanism in human cancer.","authors":"Xiaosi Gu, Xin Hu, Sijia Zhang, Xiaoyu Zhang, Yong Wang, Lianlian Li","doi":"10.3389/fmolb.2025.1540048","DOIUrl":"10.3389/fmolb.2025.1540048","url":null,"abstract":"<p><p>HOXC13 antisense RNA (HOXC13-AS, also known as HOXC-AS5) is a long non-coding RNA that is expressed abnormally in various types of tumors and is closely related to clinical staging, clinical pathological features, and patient survival. HOXC13-AS is involved in the occurrence and development of tumors, affecting cell proliferation, migration, invasion, epithelial-mesenchymal transition, and tumor growth. This review summarizes the clinical significance of HOXC13-AS as a biomarker for human tumor diagnosis and prognosis and outlines the function and molecular regulation mechanism of HOXC13-AS in various types of cancer, including nasopharyngeal carcinoma, breast cancer, oral squamous cell carcinoma, glioma, and cervical cancer. Overall, this review emphasizes the potential of HOXC13-AS as a human tumor predictive biomarker and therapeutic target, paving the way for its clinical application.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1540048"},"PeriodicalIF":3.9,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11839424/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143467641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of potential oxidative biomarkers in the prognosis of intracerebral hemorrhage and the exploration antioxidants as possible preventive and treatment options.","authors":"Jiayong Yao, Xiaohong Dai, Xueping Yv, Lei Zheng, Jia Zheng, Binglin Kuang, Wei Teng, Weiwei Yu, Mingyue Li, Hongtao Cao, Wei Zou","doi":"10.3389/fmolb.2025.1541230","DOIUrl":"10.3389/fmolb.2025.1541230","url":null,"abstract":"<p><p>Intracerebral hemorrhage (ICH) is a non traumatic hemorrhage that occurs in a certain part of the brain. It usually leads to brain cell damage. According to a large number of experimental research, oxidative stress is an important pathophysiological processes of cerebral hemorrhage. In this paper, we aim to determine how changes in oxidative stress biomarkers indicate the damage degree of cerebral hemorrhage, and to explore and summarize potential treatments or interventions. We found that patients with cerebral hemorrhage are characterized by increased levels of oxidative stress markers, such as total malondialdehyde (MDA), F2 isoprostaglandin, hydroxynonenal, myeloperoxidase and protein hydroxyl. Therefore, the changes of oxidative stress caused by ICH on these markers can be used to evaluate and diagnose ICH, predict its prognosis, and guide preventive treatment to turn to antioxidant based treatment as a new treatment alternative.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1541230"},"PeriodicalIF":3.9,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11832355/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143448766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synergistic effects of mutation and glycosylation on disease progression.","authors":"Shodai Suzuki, Motoyuki Itoh","doi":"10.3389/fmolb.2025.1550815","DOIUrl":"10.3389/fmolb.2025.1550815","url":null,"abstract":"<p><p>Glycosylation, a post-translational modification, plays a crucial role in proper localization and function of proteins. It is regulated by multiple glycosyltransferases and can be influenced by various factors. Inherited missense mutations in glycosylated proteins such as NOTCH3, Low-density lipoprotein receptor (LDLR), and Amyloid precursor protein (APP) could affect their glycosylation states, leading to cerebral small vessel disease, hypercholesterolemia, and Alzheimer's disease, respectively. Additionally, physiological states and aging-related conditions can affect the expression levels of glycosyltransferases. However, the interplay between mutations in glycosylated proteins and changes in their glycosylation levels remains poorly understood. This mini-review summarizes the effects of glycosylation on transmembrane proteins with pathogenic mutations, including NOTCH3, LDLR, and APP. We highlight the synergistic contributions of missense amino acids in the mutant proteins and alterations in their glycosylation states to their molecular pathogenesis.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1550815"},"PeriodicalIF":3.9,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11832388/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143448743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}