Integrative biology : quantitative biosciences from nano to macro最新文献

{"title":"Integrated phosphoproteome and transcriptome data-driven analysis of major transcription-regulatory phosphosites in NFIL3.","authors":"Vaishnavi Gopalakrishnan, Althaf Mahin, Amal Fahma, Afreen Khanum, Sowmya Soman, Rajesh Raju","doi":"10.1093/intbio/zyag020","DOIUrl":"https://doi.org/10.1093/intbio/zyag020","url":null,"abstract":"<p><p>Nuclear factor interleukin-3-regulated protein (NFIL3) is a transcription factor involved in the regulation of circadian rhythms and immune crosstalk. The transcriptional repressive and activational roles that influence cytokine expressions and tumor microenvironment have made NFIL3 a therapeutic target for several diseases. While protein-level functions of NFIL3 are widely explored, the molecular details regarding phospho-signals regulating NFIL3 and their functional significance are underexplored. To interpret the phosphoregulatory patterns of NFIL3, we conducted an extensive literature survey for mass-spectrometry-based cellular phosphoproteomics datasets with representation of NFIL3 phosphosites. From the compiled list of 656 cellular profiles and 116 datasets with differential expression, Ser301 and Ser353 of NFIL3 were identified as the predominant phosphosites, accounting for the majority of NFIL3 phosphosignals. Further, we explored the coregulated phosphosites in the interacting partners and transcription factors associated with NFIL3. With our integrative phosphoproteomics and the IL-4 dependent transcriptome dataset analysis, we report Ser301 and Ser353 as positively co-occurring phosphorylations in NFIL3 that essentially regulate its transcriptional activity. Further, we also unveil Mitogen-activated protein kinase 14 (MAPK14) as a high-confidence upstream kinase that can phosphorylate Ser301. This study identifies novel coregulation expression patterns and highlights regulatory phosphosites, establishing the foundation for future exploration of the NFIL3-associated dark phosphoproteome.</p>","PeriodicalId":520649,"journal":{"name":"Integrative biology : quantitative biosciences from nano to macro","volume":"18 ","pages":""},"PeriodicalIF":1.4,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149122726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated bioinformatics analysis reveals cytokine dysregulation, pathway alterations, and machine learning identification of diagnostic biomarkers in sepsis.","authors":"Weili Jiang, Jianning Rong, Wenwen Han, Jianjiang Fang","doi":"10.1093/intbio/zyag010","DOIUrl":"10.1093/intbio/zyag010","url":null,"abstract":"<p><p>Sepsis, a life-threatening dysregulated host response to infection, involves complex cytokine signaling. Comprehensive bioinformatics analysis of cytokine activity, associated pathways, and immune alterations in sepsis is warranted. Using the sepsis dataset GSE26378 from GEO, we analyzed differential cytokine pathway activity with ssGSEA and identified differentially expressed genes (DEGs). Cytokine-related genes (CRGs) were extracted and overlapped with DEGs. Protein-Protein Interaction (PPI) network analysis and functional enrichment were performed on differentially expressed CRGs. Cytokine activity scores and pathway activities were quantified using Gene Set Variation Analysis (GSVA). Immune cell infiltration was assessed with MCP-counter. Machine learning algorithms (Random Forest, LASSO, SVM) identified diagnostic biomarkers, validated using an independent dataset (GSE26440) and ROC analysis. Cytokine/cytokine receptor pathways were significantly upregulated in sepsis. We identified 617 DEGs and 46 differentially expressed CRGs. Cytokine activity scores were significantly elevated in sepsis and strongly correlated with heightened activity in inflammatory pathways (e.g. TLR, IL-1R, NF-κB, JAK/STAT, hypoxia) and metabolic pathways (e.g. glycolysis, PI3K/AKT/mTOR). Immune analysis showed decreased T cells, NK cells, B cells, and cytotoxic lymphocytes, alongside increased neutrophils and endothelial cells; neutrophil infiltration positively correlated with cytokine scores. Machine learning identified four core genes (C3AR1, XCL1, CSF2RA, IL2RB), consistently dysregulated in sepsis across datasets and demonstrating robust diagnostic accuracy. This integrated bioinformatics study indicates heightened cytokine activity, profound alterations in inflammatory and metabolic pathways, and a dysregulated immune cell landscape in sepsis. The identified hub genes and the four-gene biomarker panel show potential as diagnostic tools, offering insights into sepsis pathophysiology. Insight box This study integrates multi-omics bioinformatics (ssGSEA, GSVA, PPI, immune deconvolution) and machine learning (RF, LASSO, SVM) to dissect sepsis pathophysiology. Innovatively, we quantify cytokine pathway hyperactivity, linking it to inflammatory/metabolic dysregulation (TLR, NF-κB, glycolysis) and immune imbalance. A novel four-gene panel (C3AR1, XCL1, CSF2RA, IL2RB) was identified and validated as a robust diagnostic biomarker, bridging cytokine signaling with clinical utility. The findings provide mechanistic insights into sepsis-driven immune-metabolic crosstalk and offer translational potential for early diagnosis and targeted therapy.</p>","PeriodicalId":520649,"journal":{"name":"Integrative biology : quantitative biosciences from nano to macro","volume":"18 ","pages":""},"PeriodicalIF":1.4,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148177449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"METTL3-m6A-mediated downregulation of IGFBP6 accelerates atherosclerotic plaque formation through GPX4-induced ferroptosis.","authors":"Zhenzhen Liu, Yanru He, Wenjing Zhu","doi":"10.1093/intbio/zyag022","DOIUrl":"https://doi.org/10.1093/intbio/zyag022","url":null,"abstract":"<p><p>Insulin-like growth factor binding protein 6 (IGFBP6) is thought to be associated with the progression of atherosclerosis (AS). However, whether IGFBP6 is involved in ferroptosis, a key biological process, in the progression of AS remains unclear. In this study, IGFBP6 expression was downregulated in oxidized low-density lipoprotein (ox-LDL)-treated human umbilical vein endothelial cells (HUVECs). Overexpression of IGFBP6 inhibited reactive oxygen species (ROS) production, reduced Fe2+ concentration and and inflammatory factor levels, and increased Glutathione (GSH) content in ox-LDL-treated HUVECs. Ferrostatin-1 (Fer-1), an inhibitor of ferroptosis, reversed IGFBP6 silencing induced ferroptosis of HUVECs. Mechanistic studies revealed that IGFBP6 is a target of Methyltransferase-like protein 3 (METTL3) that mediates N6-methyladenosine (m6A) modification, and YTH N6-methyladenosine RNA binding protein 2 (YTHDF2) recognizes and promotes METTL3-m6A-mediated IGFBP6 mRNA degradation. Downregulated IGFBP6 reduces its protein level by interacting with GPX4, thereby promoting ferroptosis in HUVECs. In addition, APOE-/- mice fed with a high-fat diet were used as an AS animal model, and the results showed that endothelial cell specific METTL3 knockdown or IGFBP6 overexpression hindered the development of AS in mice. In conclusion, knockdown of METTL3 inhibited the degradation of IGFBP6 mRNA in a YTHDF2 dependent manner, thereby inhibiting GPX4-mediated ferroptosis and alleviating AS progression. Insight Box This study provided new molecular targets for the effective treatment of AS. In this study, we constructed an AS cell model and an AS mouse model to explore whether METTL3 affects ferroptosis of HUVECs by regulating IGFBP6 expression through m6A modification through gain of function and loss of function experiments of METTL3 and IGFBP6, thus revealing the molecular mechanism of its involvement in the occurrence and development of AS. Results showed that METTL3 induced GPX4-mediated ferroptosis in HUVECs through m6A-YTHDF2-dependent downregulation of IGFBP6, thereby promoting the progression of AS. These findings suggest that interfering with the METTL3/YTHDF2/IGFBP6/GPX4 axis with small molecules or gene therapy may be a new strategy to intervene the occurrence and development of AS.</p>","PeriodicalId":520649,"journal":{"name":"Integrative biology : quantitative biosciences from nano to macro","volume":"18 ","pages":""},"PeriodicalIF":1.4,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149122784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"BMI1 facilitates Wnt signaling by epigenetic silencing of Axin2 to promote cell proliferation and migration in Hirschsprung's disease.","authors":"Zhanhu Li, Dong Chen","doi":"10.1093/intbio/zyaf011","DOIUrl":"10.1093/intbio/zyaf011","url":null,"abstract":"<p><p>Hirschsprung's disease (HSCR) is a congenital intestinal disease characterized by the loss of enteric neural crest cells. BMI1 is demonstrated to be downregulated in HSCR tissues compared to normal intestinal tissues, but it is still unclear whether BMI1 is involved in the pathogenesis of HSCR. Here, we found that BMI1 expression was downregulated in HSCR-stenosed segments (HSCR-S) cases compared with HSCR-dilated segments (HSCR-D) or control cases. Pharmacological inhibition of BMI1 using PTC-209 significantly attenuated cell proliferation, migration, and cell cycle progression in both SH-SY5Y neuroblastoma cells and primary enteric neural crest cells (ENCCs), whereas BMI1 overexpression produced the opposite effects. BMI1 binds to the promoter region of the Wnt signaling pathway inhibitor Axin2 and suppressed its transcription by increasing H2AK119ub and reducing H3K4me3 at the Axin2 promoter, thereby hindering Wnt signaling. Moreover, overexpression of Axin2 decreased cell proliferation, migration and cell cycle progression. Treatment with HY-122816 (a Wnt signaling pathway agonist) reversed the inhibitory effects of PTC-209 on cell proliferation, migration, and cell cycle progression. Additionally, BMI1 upregulation promoted ganglion cell proliferation in Ednrb-/- mice. In conclusion: BMI1 facilitated Wnt signaling by mediating epigenetic silencing of Axin2, thereby promoting cell proliferation and migration in HSCR. Clinically, BMI1 expression was downregulated in HSCR-S cases compared with HSCR-D or control cases. Moreover, BMI1 was shown for the first time to promote cell proliferation, migration, and cell cycle progression in ENCCs. Molecular level probing revealed that BMI1 binds to the promoter region of Axin2, an inhibitor of the Wnt signaling pathway, and inhibited Axin2 transcription by increasing H2AK119ub and decreasing H3K4me3 in the Axin2 promoter, thereby hindering Wnt signaling. This study revealed that the BMI1/Axin2/Wnt axis may play an important role in the pathogenesis of HSCR.</p>","PeriodicalId":520649,"journal":{"name":"Integrative biology : quantitative biosciences from nano to macro","volume":"17 ","pages":""},"PeriodicalIF":1.4,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144532819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of novel zinc-binding inhibitors against key microbial metallohydrolase DapE in Klebsiella pneumoniae: an integrated ligand-based virtual screening, molecular docking, molecular dynamics, and MM/PBSA approach.","authors":"Rhitam Biswas, Anand Anbarasu","doi":"10.1093/intbio/zyaf018","DOIUrl":"10.1093/intbio/zyaf018","url":null,"abstract":"<p><p>Klebsiella pneumoniae (K. pneumoniae) has emerged as a prominent multidrug-resistant pathogen in healthcare settings and is ranked among the top three critical priority pathogens by the World Health Organization. Owing to the surge in antibiotic resistance and resulting treatment failures, there is an urgent need for alternative therapeutic approaches. N-succinyl-L, L-diaminopimelic acid desuccinylase (DapE), a crucial metalloenzyme in the lysine biosynthesis pathway in K. pneumoniae, is essential for protein synthesis and the cross-linking of the bacterial peptidoglycan cell wall. The remarkable conservation of DapE across diverse bacterial species makes it a promising target for combating drug resistance. In this study, 400 analogues were screened using virtual screening to evaluate their pharmacokinetic, toxicological, and bioactive properties. Fifty-two compounds meeting these criteria were selected for molecular docking analysis. Among these, five top-ranking compounds were identified based on docking scores, and two, ZINC262925003 (-7.1 kcal/mol) and ZINC237355153 (-7.0 kcal/mol), were selected due to their strong catalytic zinc-binding interactions at the active site. Extensive validation through 250 ns molecular dynamics simulation and Molecular Mechanics Poisson-Boltzmann Surface Area (MM/PBSA) analysis revealed high structural stability and robust binding interactions for these complexes. These findings highlight their potential as therapeutic agents against DapE, necessitating further validation through in vitro and in vivo studies. Insight Box The study employs an integrated computational approach for identifying potential zinc-binding inhibitors against Klebsiella pneumoniae's DapE (KpDapE). In recent times, antimicrobial resistance has become a global challenge in treating bacterial infections. DapE, a metalloenzyme in the lysine biosynthesis pathway in K. pneumoniae, is essential for protein synthesis and the cross-linking of the bacterial peptidoglycan cell wall. DapE is a promising drug target to develop a new class of drugs. In this study, 400 L-Captopril analogues were screened, identifying two candidates as potent leads. Molecular docking and dynamics simulations revealed that ZINC262925003 and ZINC237355153 had significant binding affinity and stable interactions with KpDapE, supported by RMSD, RMSF, and binding-free energy analyses. This suggests that both these compounds could be potent inhibitors for KpDapE.</p>","PeriodicalId":520649,"journal":{"name":"Integrative biology : quantitative biosciences from nano to macro","volume":"17 ","pages":""},"PeriodicalIF":1.4,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145093396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vitro-induced cancer-associated fibroblasts-derived Exosomal miRNA-224-5p targets PTEN to reduce cisplatin (DDP) sensitivity in colorectal cancer.","authors":"Xiao Wu, Pengcheng Ma, Ming Zhang, Ling Wang, Aijun Wang, Yuchuan Yan, Hongyu Wang, Chao Zhang, Junwei Feng","doi":"10.1093/intbio/zyaf022","DOIUrl":"10.1093/intbio/zyaf022","url":null,"abstract":"<p><strong>Background: </strong>Cancer-associated fibroblasts (CAFs)-derived exosomes promote tumor malignancy and confer chemotherapy resistance. However, their mechanistic roles in colorectal cancer (CRC) remain incompletely understood.</p><p><strong>Methods: </strong>Human normal colon fibroblasts were induced into CAFs using CRC cell-conditioned medium and identified by immunofluorescence. Exosomes were isolated from CAFs and characterized by Western blot, DLS analysis and cell uptake experiment. qPCR was employed to detect miRNA-224-5p expression in CAFs-derived exosomes. CCK-8 and comet assays were conducted to evaluate miRNA-224-5p's effect on cisplatin (DDP) resistance in CRC. TargetScan predicted miRNA-224-5p's downstream targets, with luciferase assays validating its interaction with PTEN. Overexpression experiments elucidated miRNA-224-5p's mechanism in DDP resistance via PTEN regulation.</p><p><strong>Results: </strong>miRNA-224-5p was highly expressed in CAFs-derived exosomes. Functional assays revealed that exosomal miRNA-224-5p from CAFs promoted DDP resistance in CRC cells while suppressing DNA damage and apoptosis. Mechanistically, PTEN was identified as a direct target of miRNA-224-5p, through which it enhanced DDP resistance.</p><p><strong>Conclusion: </strong>This study demonstrates that CAFs-derived exosomal miRNA-224-5p promotes DDP resistance in CRC by targeting PTEN, suggesting miRNA-224-5p as a potential therapeutic target for improving CRC treatment outcomes. Insight box MiRNA-224-5p was highly expressed in CAFs-derived exosomes. Functional assays revealed that exosomal miRNA-224-5p from CAFs promoted DDP resistance in CRC cells while suppressing DNA damage and apoptosis. PTEN was identified as a direct target of miRNA-224-5p, through which it enhanced DDP resistance.</p>","PeriodicalId":520649,"journal":{"name":"Integrative biology : quantitative biosciences from nano to macro","volume":"17 ","pages":""},"PeriodicalIF":1.4,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145696192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of a 3D in vitro model to investigate sprouting angiogenesis under hydrostatic pressure stimulation.","authors":"Dunja Al-Nuaimi, Wenle Yan, Edoardo Mazza, Costanza Giampietro","doi":"10.1093/intbio/zyaf021","DOIUrl":"10.1093/intbio/zyaf021","url":null,"abstract":"<p><p>Angiogenesis is tightly regulated by the mechanical and biochemical cues of the microenvironment. To investigate the mechanobiological regulation of endothelial cells, we developed a 3D in vitro bioreactor that enables precise, leak-free application of hydrostatic pressure to endothelialized collagen I channels. Using this platform, we seeded primary human umbilical vein endothelial cells and primary human aortic endothelial cells at optimized densities and achieved reproducible channel endothelialization. We demonstrate that sufficient protein and RNA can be extracted from single channels, enabling downstream analysis such as Western blotting and RT-qPCR. Immunofluorescent staining revealed nuclear localization of YAP in angiogenic sprouts, a feature previously observed only in 2D cultures. This confirms this model ability to recapitulate pressure-induced YAP activation also in 3D. Our findings support the feasibility of this platform for mechanobiological studies and highlight its potential for investigating angiogenic signalling under controlled pressure conditions. Insight Box A reusable 3D bioreactor enables controlled hydrostatic pressure on endothelial cells within collagen I channels. This model reveals pressure-induced YAP nuclear localization in angiogenic sprouts and supports molecular analysis from single channels, bridging mechanobiology with in vitro vascular modelling.</p>","PeriodicalId":520649,"journal":{"name":"Integrative biology : quantitative biosciences from nano to macro","volume":"17 ","pages":""},"PeriodicalIF":1.4,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145446873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Machine learning applications in colorectal cancer: from early detection to personalized treatment.","authors":"Shaik Yasmin Tabasum, C Valli Nachiyar, Swetha Sunkar","doi":"10.1093/intbio/zyaf013","DOIUrl":"10.1093/intbio/zyaf013","url":null,"abstract":"<p><p>Colorectal cancer (CRC) is a significant health challenge in the world, with incidence being increasingly reported among the young population. Machine learning, therefore, is revolutionizing care in CRC, including providing advancements in early detection, staging, recurrence prediction, and individualized medicine. Techniques for analysis include support vector machines, random forests, and neural networks, which allow complex analyses of datasets, including genetic profiles and imaging data, with an improvement in diagnostic accuracy and treatment outcomes. Machine learning-driven personalized treatment strategies empower clinicians to tailor therapies to individual patients, optimizing efficacy while reducing side effects. However, integration of Machine learning (ML) in CRC management faces challenges like data quality, validation, and smooth adaptation into clinical workflow. Overcoming these barriers through multi-institutional collaboration and strong validation frameworks will be essential to unlock the full potential of ML. Advancement in research will enable the transformation of CRC care to provide more accurate diagnoses and targeted treatments, ultimately changing patient outcomes. Insight box This review examines the transformative impact of machine learning (ML) in colorectal cancer (CRC) research and care. By integrating multi-omics, radiomics, and clinical data, ML models outperform traditional diagnostic and prognostic methods, enabling precise risk prediction, personalized treatment, and early recurrence detection. The amalgamation of supervised learning, neural networks, and deep learning yields actionable insights that improve patient outcomes and address unmet needs in CRC management. The review also discusses solutions to challenges such as data standardization, ethics, and clinical workflow integration, offering a roadmap for real-world ML adoption. This work highlights the synergy between computational advances and oncology, providing a forward-thinking framework for CRC care.</p>","PeriodicalId":520649,"journal":{"name":"Integrative biology : quantitative biosciences from nano to macro","volume":"17 ","pages":""},"PeriodicalIF":1.4,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144693092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-proteomics investigation of the early response to X-rays and carbon ion irradiations of HeLa cells.","authors":"Ousseynou Ben Diouf, Antoine Gilbert, Benoit Bernay, Mamadou Soumboundou, Cheikh Sall, François Chevalier","doi":"10.1093/intbio/zyaf008","DOIUrl":"10.1093/intbio/zyaf008","url":null,"abstract":"<p><p>Despite the considerable decline of cervical cancer incidence in developed countries, the disease remains a public health problem in low-income and middle-income countries due to the low popularity of human papillomavirus vaccination and cervical cancer screening. Mainly treated with radiotherapy, the number of recurrences linked to radioresistance increases in women suffering from this disease and constitutes major obstacle. Here, we perform a combined proteomic and phosphoproteomic profiling of HeLa cervical cancer cells after in vitro treatment with X-rays and carbon ions. We observed differential and extensive alterations at the proteins and phosphoproteins levels. In total, we observed 96 and 102 differentially expressed proteins (DEPs) after X-rays and C-ions irradiation, respectively. For phosphoproteins, our results revealed 21 and 41 DEPs in response to C-ions and X-rays ionizing radiation respectively. Furthermore, our study revealed several mechanisms significantly activated by cells in response to ionizing radiation, potentially related to cancer radioresistance, including sister chromatid segregation, rRNA processing, ribosomal large subunit biogenesis, positive regulation of phagocytosis, engulfment, peptidase regulatory activity and negative regulation of ERK1/2 cascade. We also identified three proteins IPM3, DUSP3 and COQ7, oppositely expressed across the C-ions and X-rays groups while MX2 phosphorylation was downregulated in both radiation qualities. Finally, our study revealed a specific kinase signature, associated with Hela cells radioresistance: CDK5, MTOR and CDK2 kinases were predicted in the group of X-rays irradiation while CDK1, PLK1 SRC and MAPK1 kinases were predicted in the group of C-ions irradiation. Taken together, these findings could help to define new potential pathways and biomarkers to be targeted in the treatment of cervical cancer. Insight Box Statement of Integration, Innovation and Insight In this study, a robust proteomic and phospho-proteomic strategy was developed in order to display HELA cells responses to radiations. Two time points were selected to highlight the early responses of cells, following irradiation with low and high LET. CDK1, SRC, MAPK1 kinases were predicted to be activated in response to carbon ions irradiation, while CDK5, MTOR, ATM kinases were predicted in response to X-rays. Several accessions, playing pivotal role in cell proliferation and resistance, were upregulated in X-rays irradiated cells and down regulated in carbon ions irradiated cells. This study gives an accurate picture of molecular events linked with HELA cells radioresistance and offer potential drug targets for optimization of cervical cancer radiotherapy.</p>","PeriodicalId":520649,"journal":{"name":"Integrative biology : quantitative biosciences from nano to macro","volume":"17 ","pages":""},"PeriodicalIF":1.4,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144328408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The diagnosis and prognostic value and biological function of annexin A2 in hepatocellular carcinoma: a bioinformatic and experimental study.","authors":"Ya Li, Huhu Zhang, Fulin Sun, Chunjuan Yu, Shuyao Jiang, Lina Yang","doi":"10.1093/intbio/zyaf017","DOIUrl":"10.1093/intbio/zyaf017","url":null,"abstract":"<p><p>Annexin A2 (ANXA2) is a Annexin family proteins member that plays a role in regulating cell growth and signal transduction pathways. However, its role in hepatocellular carcinoma (HCC) remains incompletely elucidated. We used bioinformatics methods to analyze the expression, diagnosis and prognostic value of ANXA2 in HCC using data from the TCGA, GTEx, GEO, HCCDB, HPA databases. Next, we predicted ANXA2-associated proteins and constructed a protein-protein interaction network via the STRING database. Furthermore, we obtained the biological processes associated with ANXA2 in HCC through GO, KEGG and GSEA enrichment analysis. Finally, CCK8, wound healing, and transwell were used to verify these biological processes in HCCLM3 cell lines. Insight box ANXA2 is highly expressed in a variety of tumors, with significantly higher levels in HCC than in normal tissues. ANXA2 expression is positively correlated with T stage, histologic grade, residual tumor, pathologic stage, tumor status and fibrosis ishak score in HCC, and high ANXA2 expression suggests a poorer prognosis. Additionally, ANXA2 has diagnostic value in HCC. Its expression is closely associated with S100A family proteins and immune infiltration. Enrichment analysis showed that high ANXA2 expression activates biological processes such as epithelial-mesenchymal transition (EMT), NF-κB and Wnt signaling pathways. The results of cell experiment were consistent with bioinformatics analysis. Our study explored the role of ANXA2 in the occurrence and development of HCC, which may provide reference for the treatment of HCC.</p>","PeriodicalId":520649,"journal":{"name":"Integrative biology : quantitative biosciences from nano to macro","volume":"17 ","pages":""},"PeriodicalIF":1.4,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144986338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}