Frontiers in Molecular Biosciences最新文献

{"title":"Calcium-dependent adhesion protein CDH18, a potential biomarker for prognosis in uterine corpus endometrial carcinoma.","authors":"Xiaoxuan Tang, Shanxing Dang, Jie Qiu, Ruilan Zhou, Jing Ling, Limei Zhang, Xiaopeng Peng, Qingyun Li, Jin Liu, Wei Liao, Qingxiu Mei, Miao Xie, Yehong Sun, Jianmei Huang, Xuelian Du, Wencong Song","doi":"10.3389/fmolb.2025.1530253","DOIUrl":"10.3389/fmolb.2025.1530253","url":null,"abstract":"<p><strong>Background: </strong>Uterine corpus endometrial carcinoma (UCEC) is one of the most common cancers in women, yet lacks specific and sensitive tumor markers for diagnosis, as traditional markers like CA125 show limited specificity. This study investigates the clinical significance and prognostic value of CDH18, a calcium-dependent adhesion protein linked to tumor progression, in UCEC.</p><p><strong>Methods: </strong>Clinical data from UCEC patients were sourced from The Cancer Genome Atlas (TCGA) database. Pan-cancer analysis, differential expression examination, and survival analysis were conducted to investigate the differential expression of the calcium associated protein-CDH18 and its prognostic relevance. CDH18 mutations in UCEC were examined using the cBioPortal database. Additional analyses included functional enrichment, tumor mutational burden, tumor microenvironment (TME) estimates via ESTIMATE, and immune infiltration assessment to clarify CDH18's potential mechanisms in UCEC. Drug sensitivity testing was utilized to identify more suitable therapeutic options for patients. Immunofluorescence staining (IF) and Real-Time Polymerase Chain Reaction techniques (RT-PCR) confirmed CDH18 expression in UCEC tumor.</p><p><strong>Results: </strong>CDH18 expression was markedly increased in UCEC and showed a significant association with poorer prognosis, which was confirmed by our IF and RT-PCR results. Thirteen mutation sites were identified, and survival analysis showed that patients with higher CDH18 expression had shorter overall survival. The expression of CDH18 was confirmed to be an independent predictor of overall survival by multivariate COX regression analysis. Additionally, a predictive nomogram model was developed to accurately forecast outcomes for individuals with UCEC. Correlation analysis revealed that CDH18 expression exhibited a negative correlation with CD8 T cell levels and a positive correlation with resting NK cell and macrophage M2 levels. In the group with high CDH18 expression, the IC50 values for (5Z)-7-Oxozeaenol, AG-014699, CEP-701, Mitomycin C, PD-0325901, PD-0332991, PHA-665752, SL 0101-1, and SN-38 were notably elevated.</p><p><strong>Conclusion: </strong>CDH18 is a novel promising biomarker in UCEC, uniquely associating tumor progression, immune modulation, and chemotherapy resistance, offering enhanced prognostic accuracy and guiding individualized therapeutic strategies for improved patient outcomes.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1530253"},"PeriodicalIF":3.9,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11864935/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143523050","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":"Simulations of pH and thermal effects on SARS-CoV-2 spike glycoprotein.","authors":"Ziyuan Niu, Georgios Kementzidis, Miriam Rafailovich, Marcia Simon, Evangelos Papadopoulos, Bertal H Aktas, Yuefan Deng","doi":"10.3389/fmolb.2025.1545041","DOIUrl":"10.3389/fmolb.2025.1545041","url":null,"abstract":"<p><p>We performed triplicate and long-time all-atom molecular dynamics simulations to investigate the structures and dynamics of the SARS-CoV-2 spike glycoprotein (S-protein) for a broad range of pH = 1 through 11 and temperatures of 3°C through 75°C. This study elucidates the complex interplay between pH and thermal effects on S-protein structures, with implications for its behavior under diverse conditions, and identifies the RBD as a primary region of the structural deviations. We found: 1) Structural deviations in the S-protein backbone at pH = 1 are 210% greater than those at pH = 7 at 75°C, with most of the deviations appearing in the receptor-binding domain (RBD). Smaller structural changes are observed at pH = 3 and 11. 2) The pH and thermal conditions impact on the protein structures: substantial acidic and basic conditions expand the protein's solvent exposure, while high heat contracts. This effect is primarily pH-driven at extreme acidity and thermo-driven at moderate pH. 3) The Gibbs free energy landscape reveals that pH as the main driver of structural changes. 4) The parametrized methods enable the predictions of the S-protein properties at any reasonable pH and thermal conditions without explicit MD simulations.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1545041"},"PeriodicalIF":3.9,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11850259/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143499813","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":"IL-6/GATA2/SERPINE1 pathway is implicated in regulating cellular senescence after acute kidney injury.","authors":"Hongshuang Su, Xiaoxi Lin, Ayinuer Paredong, Congcong Yao, Yan Zhang, Mengke Geng, Yuqian Guan, Lichao Gong, Feng Jiang, Qi Lv, Songtao Shou, Heng Jin","doi":"10.3389/fmolb.2025.1538526","DOIUrl":"10.3389/fmolb.2025.1538526","url":null,"abstract":"<p><strong>Purpose: </strong>Acute kidney injury (AKI) secondary to Rhabdomyolysis syndrome represents a life-threatening complication, characterized by notably high incidence and mortality rates. The role of cellular senescence in the progression of AKI has increasingly garnered attention in recent years. Our previous research has demonstrated that remote ischemic postconditioning (RIPC) can attenuate renal cellular senescence and elevation of serum level of interleukin-6 (IL-6) induced by ischemia-reperfusion injury following crush injury. The objective of this study is to investigate the specific role of IL-6 in Rhabdomyolysis-induced AKI (RM-AKI).</p><p><strong>Methods: </strong>We established a mouse model of RM-AKI by intramuscular injection of glycerol and simulated RM-AKI at the cellular level by treating Hk-2 cells with myoglobin. Tocilizumab (TCZ), a humanized monoclonal antibody against the interleukin-6 (IL-6) receptor, is a key substance. IL-6, a multifunctional cytokine, plays a crucial role in the occurrence and development of various kidney diseases. It can promote inflammatory responses, cell proliferation, fibrosis, and other processes. TCZ exerts a protective effect on the kidneys by specifically binding to the IL-6 receptor and blocking the signal transduction of IL-6. Additionally, the levels of IL-6 were detected by employing ELISA kits. RNA sequencing analysis was performed on cells treated with myoglobin and tocilizumab. Flow cytometry was utilized to assess cell cycle distribution and the percentage of senescent cells. The expression levels of SERPINE1, GATA2, p53, and p21 were determined by real-time quantitative PCR and Western blot. Additionally, a dual-luciferase reporter gene assay was conducted to validate the binding effect of SERPINE1 and GATA2.</p><p><strong>Results: </strong>Transcriptome Analysis revealed that genes including GATA2 and SERPINE1 were downregulated in HK-2 cells following tocilizumab treatment. Inhibition of the IL-6 receptor by tocilizumab in these cells led to a reduction in cellular senescence, accompanied by decreased of the cell cycle regulatory proteins P53 and P21 in mRNA and protein levels, while alleviating cell cycle arrest. Additionally, a dual-luciferase reporter assay confirmed that GATA2 binds to the promoter of SERPINE1 (PAI-1), thereby initiating its transcription.</p><p><strong>Conclusion: </strong>The IL-6/GATA2/SERPINE1 pathway mediates cellular senescence after acute kidney injury, and inhibiting IL-6 can alleviate AKI-induced cellular senescence, providing an important basis for exploring new therapeutic strategies.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1538526"},"PeriodicalIF":3.9,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11850272/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143499340","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":"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}