Margareta Lakušić , Maik Damm , Vukašin Bjelica , Marko Anđelković , Ljiljana Tomović , Xavier Bonnet , Dragan Arsovski , Roderich D. Süssmuth , Juan J. Calvete , Fernando Martínez-Freiría
{"title":"Ontogeny, not prey availability, underlies allopatric venom variability in insular and mainland populations of Vipera ammodytes","authors":"Margareta Lakušić , Maik Damm , Vukašin Bjelica , Marko Anđelković , Ljiljana Tomović , Xavier Bonnet , Dragan Arsovski , Roderich D. Süssmuth , Juan J. Calvete , Fernando Martínez-Freiría","doi":"10.1016/j.jprot.2024.105320","DOIUrl":"10.1016/j.jprot.2024.105320","url":null,"abstract":"<div><div>Allopatric populations living under distinct ecological conditions are excellent systems to infer factors underlying intraspecific venom variation. The venom composition of two populations of <em>Vipera ammodytes</em>, insular with a diet based on ectotherms and mainland with a diet based on ectotherms and endotherms, was compared considering the sex and age of individuals. Ten toxin families, dominated by PLA<sub>2</sub>, svMP, svSP, and DI, were identified through a bottom-up approach. The venom profiles of adult females and males were similar. Results from 58 individual SDS-PAGE profiles and venom pool analysis revealed significant differences between juveniles compared to subadults and adults. Two venom phenotypes were identified: a juvenile svMP-dominated and KUN-lacking phenotype and an adult PLA<sub>2</sub>/svMP-balanced and KUN-containing phenotype. Despite differences in prey availability (and, therefore, diet) between populations, no significant differences in venom composition were found. As the populations are geographically isolated, the lack of venom diversification could be explained by insufficient time for natural selection and/or genetic drift to act on the venom composition of island vipers. However, substantial differences in proteomes were observed when compared to venoms from geographically distant populations inhabiting different conditions. These findings highlight the need to consider ecological and evolutionary processes when studying venom variability.</div></div><div><h3>Significance</h3><div>This study provides the first comprehensive analysis of the venom composition of two allopatric populations of <em>Vipera ammodytes</em>, living under similar abiotic (climate) but distinct biotic (prey availability) conditions. The ontogenetic changes in venom composition, coupled with the lack of differences between sex and between populations, shed light on the main determinants of venom evolution in this medically important snake. Seven new proteomes may facilitate future comparative studies of snake venom evolution. This study highlights the importance of considering ecological and evolutionary factors to understand snake venom variation.</div></div>","PeriodicalId":16891,"journal":{"name":"Journal of proteomics","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Drug response-based precision therapeutic selection for tamoxifen-resistant triple-positive breast cancer","authors":"Vinod S. Bisht , Deepak Kumar , Mohd Altaf Najar , Kuldeep Giri , Jaismeen Kaur , Thottethodi Subrahmanya Keshava Prasad , Kiran Ambatipudi","doi":"10.1016/j.jprot.2024.105319","DOIUrl":"10.1016/j.jprot.2024.105319","url":null,"abstract":"<div><p>Breast cancer adaptability to the drug environment reduces the chemotherapeutic response and facilitates acquired drug resistance. Cancer-specific therapeutics can be more effective against advanced-stage cancer than standard chemotherapeutics. To extend the paradigm of cancer-specific therapeutics, clinically relevant acquired tamoxifen-resistant MCF-7 proteome was deconstructed to identify possible druggable targets (<em>N</em> = 150). Twenty-eight drug inhibitors were used against identified druggable targets to suppress non-resistant (NC) and resistant cells (RC). First, selected drugs were screened using growth-inhibitory response against NC and RC. Seven drugs were shortlisted for their time-dependent (10–12 days) cytotoxic effect and further narrowed to three effective drugs (e.g., cisplatin, doxorubicin, and hydroxychloroquine). The growth-suppressive effectiveness of selected drugs was validated in the complex spheroid model (progressive and regressive). In the progressive model, doxorubicin (RC: 83.64 %, NC: 54.81 %), followed by cisplatin (RC: 76.66 %, NC: 68.94 %) and hydroxychloroquine (RC: 68.70 %, NC: 61.78 %) showed a significant growth-suppressive effect. However, in fully grown regressive spheroid, after 4th drug treatment, cisplatin significantly suppressed RC (84.79 %) and NC (40.21 %), while doxorubicin and hydroxychloroquine significantly suppressed only RC (76.09 and 76.34 %). Our in-depth investigation effectively integrated the expression data with the cancer-specific therapeutic investigation. Furthermore, our three-step sequential drug-screening approach unbiasedly identified cisplatin, doxorubicin, and hydroxychloroquine as an efficacious drug to target heterogeneous cancer cell populations.</p></div><div><h3>Significance statement</h3><p>Hormonal-positive BC grows slowly, and hormonal-inhibitors effectively suppress the oncogenesis. However, development of drug-resistance not only reduces the drug-response but also increases the chance of BC aggressiveness. Further, alternative chemotherapeutics are widely used to control advanced-stage BC. In contrast, we hypothesized that, compared to standard chemotherapeutics, cancer-specific drugs can be more effective against resistant-cancer. Although cancer-specific treatment identification is an uphill battle, our work shows proteome data can be used for drug selection. We identified multiple druggable targets and, using ex-vivo methods narrowed multiple drugs to disease-condition-specific therapeutics. We consider that our investigation successfully interconnected the expression data with the functional disease-specific therapeutic investigation and selected drugs can be used for effective resistant treatment with higher therapeutic response.</p></div>","PeriodicalId":16891,"journal":{"name":"Journal of proteomics","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1874391924002513/pdfft?md5=b8fd894e3cc744d22eedc45bed0e8399&pid=1-s2.0-S1874391924002513-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142274222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Tandem mass tag-based proteomic analysis of granulosa and theca interna cells of the porcine ovarian follicle following in vitro treatment with vitamin D3 and insulin alone or in combination","authors":"Kinga Kamińska , Bianka Świderska , Agata Malinowska , Małgorzata Grzesiak","doi":"10.1016/j.jprot.2024.105318","DOIUrl":"10.1016/j.jprot.2024.105318","url":null,"abstract":"<div><p>This study was performed to investigate the proteomic basis underlying the interaction between vitamin D<sub>3</sub> (VD) and insulin (I) within ovarian follicle using the pig as a model. Porcine antral follicles were incubated <em>in vitro</em> for 12 h with VD alone and I alone or in combination (VD + I) or with no treatment as the control (C). In total, 7690 and 7467 proteins were identified in the granulosa and theca interna compartments, respectively. Comparative proteomic analysis revealed 97 differentially abundant proteins (DAPs) within the granulosa layer and 11 DAPs within the theca interna layer. In the granulosa compartment, VD affected proteome leading to the promotion of cell proliferation, whereas I influenced mainly proteins related to cellular adhesion. The VD + I treatment induced granulosa cell proliferation probably <em>via</em> the DAPs involved in DNA synthesis and the cell cycle regulation. In the theca interna layer, VD alone or in co-treatment with I affected DAPs associated with cholesterol transport and lipid and steroid metabolic processes that was further confirmed by diminished lipid droplet accumulation.</p></div><div><h3>Significance</h3><p>The application of quantitative proteomics demonstrated for the first time the complexity of VD and I interactions in porcine ovarian follicle, providing a framework for understanding the molecular mechanisms underlying their cross-talk. Although identified DAPs were related to crucial ovarian processes, including the granulosa cell proliferation and cholesterol transport in the theca interna layer, novel molecular pathways underlying these processes have been proposed. The identified unique proteins may serve as indicators of VD and I interactions in both follicle layers, and could be useful biomarkers of ovarian pathologies characterized by impaired VD and I levels, such as polycystic ovary syndrome.</p></div>","PeriodicalId":16891,"journal":{"name":"Journal of proteomics","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1874391924002501/pdfft?md5=01ed789897643acd081eef443def7947&pid=1-s2.0-S1874391924002501-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142241651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rachel Lau , Lu Yu , Theodoros I. Roumeliotis , Adam Stewart , Lisa Pickard , Ruth Riisanes , Bora Gurel , Johann S. de Bono , Jyoti S. Choudhary , Udai Banerji
{"title":"Corrigendum to “Unbiased differential proteomic profiling between cancer-associated fibroblasts and cancer cell lines” [Journal of Proteomics (2023) Volume 288, Article number 104973]","authors":"Rachel Lau , Lu Yu , Theodoros I. Roumeliotis , Adam Stewart , Lisa Pickard , Ruth Riisanes , Bora Gurel , Johann S. de Bono , Jyoti S. Choudhary , Udai Banerji","doi":"10.1016/j.jprot.2024.105306","DOIUrl":"10.1016/j.jprot.2024.105306","url":null,"abstract":"","PeriodicalId":16891,"journal":{"name":"Journal of proteomics","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1874391924002380/pdfft?md5=7087b31f0774e725f8996eb7a2530f81&pid=1-s2.0-S1874391924002380-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142145889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Unravelling the role of NDUFAF4 in Colon Cancer: Insights from multi-omics analysis","authors":"Taimoor Riaz, Muhammad Zubair","doi":"10.1016/j.jprot.2024.105309","DOIUrl":"10.1016/j.jprot.2024.105309","url":null,"abstract":"<div><p>Colon cancer is a significant public health issue, and a deeper understanding of the molecular fundamentals [<span><span>16</span></span>] ehind is required to improve sensitivity and curability. This research explored the gene NDUFAF4 as a target of concern due to its link to a mitochondrial function and protein “Relatively of liver tumorigenesis”, which remains unclear is attributable to its inclusion into the complex I (CI) pathway. The gene ontology analysis, in turn, showed that NDUFAF4 is a key player in several critical biological phases linked to mitochondrial function and energy metabolism. Furthermore, survival analysis displayed that there was a strong correlation between NDUFAF4 expression and the patients' longevity suggesting that this factor may be important in colon cancer prognosis as well. The TCGA data proved that NDUFAF4 is elevated in colon cancer making the results of the analysis reported credible. All of the above justified the understanding of the role and importance of NDUFAF4 in treating each colon cancer patient as a molecular target. The findings help in understanding the colon cancer pathogenesis and suggest ways for developing more efficient diagnosis and treatment of the disease.</p></div><div><h3>Significance</h3><p>This research explored the gene NDUFAF4 as a target of concern due to its link to a mitochondrial function and protein “Relatively of liver tumorigenesis”, which remains unclear is attributable to its inclusion into the complex I (CI) pathway. Using a comprehensive approach to Gene Ontology analysis, Protein-Protein Interaction network modelling, survival analysis, KEGG pathway analysis, and validation using TCGA data, we identified the activities of NDUFAF4 in colon cancer. The Gene Ontology analysis, in turn, showed that NDUFAF4 is a key player in several critical biological phases linked to mitochondrial function and energy metabolism. The construction of the PPI network illustrates the interactors of NDUFAF4, the functional association protein within the cellular regulatory networks. In addition, survival analysis indicated that there was a considerable relationship between the expression of NDUFAF4 and patient survival, indicating its potential role as a prognostic factor in colon cancer. KEGG pathway analysis suggested that NDUFAF4 plays a role in thermogenesis and mitochondrial biogenesis, biological processes that should be targeted due to their implication in cellular metabolism and cancer onset. The use of TCGA information confirmed the upregulation of NDUFAF4 in colon cancer, thus making the findings of the analysis reported dependable. Overall, our study provided necessary information on the role and significance of NDUFAF4, a potential molecular target in colon cancer cases. These present findings enhance our knowledge of the pathogenesis of colon cancer and open new opportunities for designing novel diagnostic and therapeutic approaches to improve patient outcomes.</p></div>","PeriodicalId":16891,"journal":{"name":"Journal of proteomics","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1874391924002410/pdfft?md5=f0ea68db32bb49d0dd7f86a1e1d0a44a&pid=1-s2.0-S1874391924002410-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142145888","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Machine learning approach to predict blood-secretory proteins and potential biomarkers for liver cancer using omics data","authors":"Dahrii Paul, Vigneshwar Suriya Prakash Sinnarasan, Rajesh Das, Md Mujibur Rahman Sheikh, Amouda Venkatesan","doi":"10.1016/j.jprot.2024.105298","DOIUrl":"10.1016/j.jprot.2024.105298","url":null,"abstract":"<div><p>Identifying non-invasive blood-based biomarkers is crucial for early detection and monitoring of liver cancer (LC), thereby improving patient outcomes. This study leveraged computational approaches to predict potential blood-based biomarkers for LC. Machine learning (ML) models were developed using selected features from blood-secretory proteins collected from the curated databases. The logistic regression (LR) model demonstrated the optimal performance. Transcriptome analysis across 7 LC cohorts revealed 231 common differentially expressed genes (DEGs). The encoded proteins of these DEGs were compared with the ML dataset, revealing 29 proteins overlapping with the blood-secretory dataset. The LR model also predicted 29 additional proteins as blood-secretory with the remaining protein-coding genes. As a result, 58 potential blood-secretory proteins were obtained. Among the top 20 genes, 13 common hub genes were identified. Further, area under the receiver operating characteristic curve (ROC AUC) analysis was performed to assess the genes as potential diagnostic blood biomarkers. Six genes, <em>ESM1</em>, <em>FCN2</em>, <em>MDK</em>, <em>GPC3</em>, <em>CTHRC1</em> and <em>COL6A6</em>, exhibited an AUC value higher than 0.85 and were predicted as blood-secretory. This study highlights the potential of an integrative computational approach for discovering non-invasive blood-based biomarkers in LC, facilitating for further validation and clinical translation.</p></div><div><h3>Significance</h3><p>Liver cancer is one of the leading causes of premature death worldwide, with its prevalence and mortality rates projected to increase. Although current diagnostic methods are highly sensitive, they are invasive and unsuitable for repeated testing. Blood biomarkers offer a promising non-invasive alternative, but their wide dynamic range of protein concentration poses experimental challenges. Therefore, utilizing available omics data to develop a diagnostic model could provide a potential solution for accurate diagnosis. This study developed a computational method integrating machine learning and bioinformatics analysis to identify potential blood biomarkers. As a result, ESM1, FCN2, MDK, GPC3, CTHRC1 and COL6A6 biomarkers were identified, holding significant promise for improving diagnosis and understanding of liver cancer. The integrated method can be applied to other cancers, offering a possible solution for early detection and improved patient outcomes.</p></div>","PeriodicalId":16891,"journal":{"name":"Journal of proteomics","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142108597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Catia Santa , João E. Rodrigues , Ana Martinho , Vera M. Mendes , Nuno Madeira , Manuel Coroa , Vítor Santos , Sofia Morais , Miguel Bajouco , Hélder Costa , Sandra I. Anjo , Inês Baldeiras , Antonio Macedo , Bruno Manadas
{"title":"Proteomic analysis of peripheral blood mononuclear cells in first episode psychosis – Protein and peptide-centered approaches to elucidate potential diagnostic biomarkers","authors":"Catia Santa , João E. Rodrigues , Ana Martinho , Vera M. Mendes , Nuno Madeira , Manuel Coroa , Vítor Santos , Sofia Morais , Miguel Bajouco , Hélder Costa , Sandra I. Anjo , Inês Baldeiras , Antonio Macedo , Bruno Manadas","doi":"10.1016/j.jprot.2024.105296","DOIUrl":"10.1016/j.jprot.2024.105296","url":null,"abstract":"<div><p>Diagnosing patients suffering from psychotic disorders is far from being achieved with molecular support, despite all the efforts to study these disorders from different perspectives. Characterizing the proteome of easily obtainable blood specimens, such as the peripheral blood mononuclear cells (PBMCs), has particular interest in biomarker discovery and generating pathophysiological knowledge. This approach has been explored in psychiatry, and while generating valuable information, it has not translated into meaningful biomarker discovery. In this project, we report the proof-of-concept of a methodology that aims to explore further information obtained with classical proteomics approaches that is easily overlooked. PBMC samples from first-episode psychosis and control subjects were subjected to a SWATH-MS approach, and the classical protein relative quantification was performed, where 389 proteins were found to be important to distinguish the two groups. Individual analysis of the quantified peptides was also performed, highlighting peptides of unchanged proteins that were significantly altered. With the combination of protein- and peptide-centered proteomics approaches, it is possible to highlight that information about proteoforms, namely regulation at the peptide level possibly due to post-translational modifications, is routinely overlooked and that its diagnostic potential should be further explored.</p></div><div><h3>Significance</h3><p>Our exploratory findings highlight the potential of MS-based proteomics strategies, combining protein- and peptide-centered approaches, to aid clinical decision-making in first-episode psychosis, helping to establish early biomarkers for schizophrenia and other psychotic disorders. Particularly, the less popular peptide-centered approach allows the identification/measurement of overlooked modulated peptides that may have potential biomarker characteristics. The application in parallel of protein- and peptide-centered strategies is transversal to research of other diseases, potentially allowing a more comprehensive characterization of the metabolic/pathophysiological alterations related to a specific disease.</p></div>","PeriodicalId":16891,"journal":{"name":"Journal of proteomics","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142097584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zhiqiang Li , Shuli Wang , Qifeng Li , Qiuhui Lin , Chunmei Zhang , Li Xi , Yanyan Cui , Yawen Dai , Shuanghong Yin , Yu Zhang , Hui Zhang
{"title":"RNA-seq reveals the important role of transcriptional regulator DeoR1 in regulating Brucella abortus various pathways","authors":"Zhiqiang Li , Shuli Wang , Qifeng Li , Qiuhui Lin , Chunmei Zhang , Li Xi , Yanyan Cui , Yawen Dai , Shuanghong Yin , Yu Zhang , Hui Zhang","doi":"10.1016/j.jprot.2024.105297","DOIUrl":"10.1016/j.jprot.2024.105297","url":null,"abstract":"<div><p><em>Brucella</em> spp. is an intracellular bacterium that uses its transcriptional regulator DeoR1 to promote intracellular transport and survival, but the molecular mechanism remains unknown. To analyze the role of DeoR1 in the virulence of <em>B. abortus</em> and the genes regulated by DeoR1, we created a A19Δ<em>deoR1</em> mutant of <em>B. abortus</em> A19 (A19). Virulence assay was performed using a murine macrophage cell line (RAW264.7) and mice. We observed that A19Δ<em>deoR1</em> mutant is attenuated in RAW264.7 cells and mice. We performed RNA-seq whole transcriptome analysis of A19Δ<em>deoR1</em> and A19 from infected RAW264.7 cells. A total of 135 differentially expressed genes were identified, including 100 up-regulated and 35 down-regulated genes. These differentially expressed genes were involved in amino acid synthesis and metabolism, energy production and conversion, stress proteins, chaperonin, hypothetical proteins and protein of unknown function, cell wall/membrane/envelope, intracellular transporting and secretion, and transcriptional regulator. Interestingly, genes involved in the intracellular trafficking and secretion were significantly down-regulated in A19Δ<em>deoR1</em>. Furthermore, selected RNA-seq results were experimentally confirmed by qRT-PCR. Overall, these results deciphered differential phenomena associated with virulence in A19Δ<em>deoR1</em> and A19 from infected RAW264.7 cells, which provided important information for understanding the detailed role of DeoR1 in <em>Brucella</em> pathogenesis.</p></div><div><h3>Significance</h3><p>Transcriptional regulators are predominant bacterial signal transduction factors. The pathogenicity of <em>Brucella</em> is due to its ability to regulate the expression of virulence related genes. Transcriptional regulators are designed to regulate gene expression and enact an appropriate adaptive physiological response. Here, a total of 135 differentially expressed genes were identified in transcriptional regulator <em>deoR1</em> mutant.</p></div>","PeriodicalId":16891,"journal":{"name":"Journal of proteomics","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142096984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Combination of transcriptomics and proteomics for analyzing potential biomarker and molecular mechanism underlying skeletal muscle atrophy","authors":"Lin Yin , Shasha Wu , Peirong Bai , Xuena Wang","doi":"10.1016/j.jprot.2024.105283","DOIUrl":"10.1016/j.jprot.2024.105283","url":null,"abstract":"<div><h3>Background</h3><p>The skeletal muscle atrophy is prevalently occurred in numerous chronic disease complications. Despite its important clinical significance, there are currently no therapeutic drugs, so new biomarkers and molecular mechanisms need to be discovered urgently.</p></div><div><h3>Methods</h3><p>Transcriptome and proteome sequencing data were collected from normal and skeletal muscle atrophic mice. The differentially expressed genes (DEGs) and proteins (DEPs) were analyzed. Applying PPI analysis to obtain overlapping genes and proteins, which were next subjected to GO and KEGG enrichment analysis. Combined analysis of transcriptomics and proteomics was performed to get key genes that were simultaneously found in GO and KEGG enrichment results. Subsequently, RT-qPCR and immunofluorescence were constructed to verify the expression of screened key genes.</p></div><div><h3>Results</h3><p>By combination of transcriptomics, proteomics and RT-qPCR results, we identified 14 key genes (<em>Cav1</em>, <em>Col3a1</em>, <em>Dnaja1</em>, <em>Postn</em>, <em>Ptges3</em>, <em>Cd44</em>, <em>Clec3b</em>, <em>Igfbp6</em>, <em>Lamc1</em>, <em>Alb</em>, <em>Itga6</em>, <em>Mmp2</em>, <em>Timp2</em> and <em>Cd9</em>) that were markedly different in atrophic mice. Single-gene GSEA and immunofluorescence suggested <em>Cd9</em> was probably the biomarker for skeletal muscle atrophy.</p></div><div><h3>Conclusions</h3><p>Our study hinted that <em>Cd9</em> was potential biomarker and may interfere with skeletal muscle atrophy through process of aerobic respiration, oxidative phosphorylation, and metabolism of amino acids and fatty acids.</p></div><div><h3>Significance</h3><p>The present study holds the subsequent significance:</p><p>Frist, we investigated biomarkers for skeletal muscle atrophy using multi-omics approach. A total of 14 genes were markedly different in skeletal muscle atrophic mice. We finally found <em>Cd9</em> is a potential biomarker for skeletal muscle atrophy. Our work presents novel biomarkers and potential regulatory mechanisms for the early detection and intervention of muscle atrophy.</p></div>","PeriodicalId":16891,"journal":{"name":"Journal of proteomics","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S187439192400215X/pdfft?md5=9cfdcab1399585f8c87bdb693fc46387&pid=1-s2.0-S187439192400215X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142046811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}