International Journal of Biochemistry & Cell Biology最新文献

{"title":"The inositol-requiring enzyme 1 (IRE1) endoplasmic reticulum stress pathway promotes MDA-MB-231 cell survival and renewal in response to the aryl-ureido fatty acid CTU","authors":"Md Khalilur Rahman ,&nbsp;Balasubrahmanyam Umashankar ,&nbsp;Hassan Choucair ,&nbsp;Kirsi Bourget ,&nbsp;Tristan Rawling ,&nbsp;Michael Murray","doi":"10.1016/j.biocel.2024.106571","DOIUrl":"https://doi.org/10.1016/j.biocel.2024.106571","url":null,"abstract":"<div><p>Current treatment options for triple-negative breast cancer (TNBC) are limited to toxic drug combinations of low efficacy. We recently identified an aryl-substituted fatty acid analogue, termed CTU, that effectively killed TNBC cells in vitro and in mouse xenograft models in vivo without producing toxicity. However, there was a residual cell population that survived treatment. The present study evaluated the mechanisms that underlie survival and renewal in CTU-treated MDA-MB-231 TNBC cells. RNA-seq profiling identified several pro-inflammatory signaling pathways that were activated in treated cells. Increased expression of cyclooxygenase-2 and the cytokines IL-6, IL-8 and GM-CSF was confirmed by real-time RT-PCR, ELISA and Western blot analysis. Increased self-renewal was confirmed using the non-adherent, in vitro colony-forming mammosphere assay. Neutralizing antibodies to IL-6, IL-8 and GM-CSF, as well as cyclooxygenase-2 inhibition suppressed the self-renewal of MDA-MB-231 cells post-CTU treatment. IPA network analysis identified major NF-κB and XBP1 gene networks that were activated by CTU; chemical inhibitors of these pathways and esiRNA knock-down decreased the production of pro-inflammatory mediators. NF-κB and XBP1 signaling was in turn activated by the endoplasmic reticulum (ER)-stress sensor inositol-requiring enzyme 1 (IRE1), which mediates the unfolded protein response. Co-treatment with an inhibitor of IRE1 kinase and RNase activities, decreased phospho-NF-κB and XBP1s expression and the production of pro-inflammatory mediators. Further, IRE1 inhibition also enhanced apoptotic cell death and prevented the activation of self-renewal by CTU. Taken together, the present findings indicate that the IRE1 ER-stress pathway is activated by the anti-cancer lipid analogue CTU, which then activates secondary self-renewal in TNBC cells.</p></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"171 ","pages":"Article 106571"},"PeriodicalIF":4.0,"publicationDate":"2024-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1357272524000621/pdfft?md5=8a183f8ad408d77039630f4824e9dd4d&pid=1-s2.0-S1357272524000621-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140554651","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":"INHBA regulates Hippo signaling to confer 5-FU chemoresistance mediated by cellular senescence in colon cancer cells","authors":"Zhan Zhang ,&nbsp;Lili Chen ,&nbsp;Qiao Yang ,&nbsp;Xiaowan Tang ,&nbsp;Jianhua Li ,&nbsp;Guangwen Zhang ,&nbsp;Youqun Wang ,&nbsp;Hui Huang","doi":"10.1016/j.biocel.2024.106570","DOIUrl":"https://doi.org/10.1016/j.biocel.2024.106570","url":null,"abstract":"<div><p>Colon cancer has become a global public health challenge, and 5-Fluorouracil (5-FU) chemoresistance is a major obstacle in its treatment. Chemoresistance can be mediated by therapy-induced cellular senescence. This study intended to investigate mechanisms of INHBA (inhibin A) in 5-FU resistance mediated by cellular senescence in colon cancer. Bioinformatics analysis of INHBA expression in colon cancer tissues, survival analysis, and correlation analysis of cellular senescence markers were performed. The effects of INHBA on the biological characteristics and 5-FU resistance of colon cancer cells were examined through loss/gain-of-function and molecular assays. Finally, a xenograft mouse model was built to validate the mechanism of INHBA <em>in vivo</em>. INHBA was upregulated in colon cancer and was significantly positively correlated with cellular senescence markers uncoupling protein 2 (UCP-2), matrix metalloproteinase-1 (MMP-1), dense and erect panicle 1 (DEP1), and p21. Cellular senescence in colon cancer mediated 5-FU resistance. Downregulation of INHBA expression enhanced 5-FU sensitivity in colon cancer cells, inhibited cell proliferation, promoted apoptosis, increased the proportion of cells in G0/G1 phase, and it resulted in a lower proportion of senescent cells and lower levels of the cellular senescence markers interleukin 6 (IL-6) and interleukin 8 (IL-8). Analysis of whether to use the pathway inhibitor Verteporfin proved that INHBA facilitated colon cancer cell senescence and enhanced 5-FU chemoresistance via inactivation of Hippo signaling pathway, and consistent results were obtained <em>in vivo</em>. Collectively, INHBA conferred 5-FU chemoresistance mediated by cellular senescence in colon cancer cells through negative regulation of Hippo signaling.</p></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"171 ","pages":"Article 106570"},"PeriodicalIF":4.0,"publicationDate":"2024-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140554652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondrial regulation of diabetic endothelial dysfunction: Pathophysiological links","authors":"Xinyi Fang ,&nbsp;Yanjiao Zhang ,&nbsp;Haoran Wu ,&nbsp;Han Wang ,&nbsp;Runyu Miao ,&nbsp;Jiahua Wei ,&nbsp;Yuxin Zhang ,&nbsp;Jiaxing Tian ,&nbsp;Xiaolin Tong","doi":"10.1016/j.biocel.2024.106569","DOIUrl":"10.1016/j.biocel.2024.106569","url":null,"abstract":"<div><p>Micro- and macrovascular complications frequently occur in patients with diabetes, with endothelial dysfunction playing a key role in the development and progression of the complications. For the early diagnosis and optimal treatment of vascular complications associated with diabetes, it is imperative to comprehend the cellular and molecular mechanisms governing the function of diabetic endothelial cells. Mitochondria function as crucial sensors of environmental and cellular stress regulating endothelial cell viability, structural integrity and function. Impaired mitochondrial quality control mechanisms and mitochondrial dysfunction are the main features of endothelial damage. Hence, targeted mitochondrial therapy is considered promising novel therapeutic options in vascular complications of diabetes. In this review, we focus on the mitochondrial functions in the vascular endothelial cells and the pathophysiological role of mitochondria in diabetic endothelial dysfunction, aiming to provide a reference for related drug development and clinical diagnosis and treatment.</p></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"170 ","pages":"Article 106569"},"PeriodicalIF":4.0,"publicationDate":"2024-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140332179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurotensin contributes to cholestatic liver disease potentially modulating matrix metalloprotease-7","authors":"Hongxia Zhao ,&nbsp;Xinbei Tian ,&nbsp;Bo Wu ,&nbsp;Ying Lu ,&nbsp;Jun Du ,&nbsp;Shicheng Peng ,&nbsp;Yongtao Xiao","doi":"10.1016/j.biocel.2024.106567","DOIUrl":"10.1016/j.biocel.2024.106567","url":null,"abstract":"<div><p>The diagnosis and treatment of biliary atresia pose challenges due to the absence of reliable biomarkers and limited understanding of its etiology. The plasma and liver of patients with biliary atresia exhibit elevated levels of neurotensin. To investigate the specific role of neurotensin in the progression of biliary atresia, the patient's liver pathological section was employed. Biliary organoids, cultured biliary cells, and a mouse model were employed to elucidate both the potential diagnostic significance of neurotensin and its underlying mechanistic pathway. In patients’ blood, the levels of neurotensin were positively correlated with matrix metalloprotease-7, interleukin-8, and liver function enzymes. Neurotensin and neurotensin receptors were mainly expressed in the intrahepatic biliary cells and were stimulated by bile acids. Neurotensin suppressed the growth and increased expression of matrix metalloprotease-7 in biliary organoids. Neurotensin inhibited mitochondrial respiration, oxidative phosphorylation, and attenuated the activation of calmodulin-dependent kinase kinase 2-adenosine monophosphate-activated protein kinase (CaMKK2-AMPK) signaling in cultured biliary cells. The stimulation of neurotensin in mice and cultured cholangiocytes resulted in the upregulation of matrix metalloprotease-7 expression through binding to its receptors, namely neurotensin receptors 1/3, thereby attenuating the activation of the CaMKK2-AMPK pathway. In conclusion, these findings revealed the changes of neurotensin in patients with cholestatic liver disease and its mechanism in the progression of the disease, providing a new understanding of the complex mechanism of hepatobiliary injury in children with biliary atresia.</p></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"170 ","pages":"Article 106567"},"PeriodicalIF":4.0,"publicationDate":"2024-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140208158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulatory T cells: Supporting lung homeostasis and promoting resolution and repair after lung injury","authors":"Morgan J. McCullough ,&nbsp;Pria G. Bose ,&nbsp;Jason R. Mock","doi":"10.1016/j.biocel.2024.106568","DOIUrl":"10.1016/j.biocel.2024.106568","url":null,"abstract":"<div><p>Regulatory T cells, characterized by their expression of the transcription factor Forkhead box P3, are indispensable in maintaining immune homeostasis. The respiratory system is constantly exposed to many environmental challenges, making it susceptible to various insults and infections. Regulatory T cells play essential roles in maintaining homeostasis in the lung and promoting repair after injury. Regulatory T cell function dysregulation can lead to inflammation, tissue damage, or aberrant repair. Research on regulatory T cell mechanisms in the lung has unveiled their influence on lung inflammation and repair mechanisms. In this review, our goal is to highlight the advances in regulatory T cell biology with respect to lung injury and resolution. We further provide a perspective that a deeper understanding of regulatory T cell interactions in the lung microenvironment in health and disease states offers opportunities for therapeutic interventions as treatments to promote lung health.</p></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"170 ","pages":"Article 106568"},"PeriodicalIF":4.0,"publicationDate":"2024-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140190373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenetic regulation of hepatocellular carcinoma progression: MicroRNAs as therapeutic, diagnostic and prognostic factors","authors":"Mehrdad Hashemi ,&nbsp;Pouria Daneii ,&nbsp;Mahya Asadalizadeh ,&nbsp;Kiana Tabari ,&nbsp;Arash Matinahmadi ,&nbsp;Seyed Shahabadin Bidoki ,&nbsp;Yasamin Sadat Mousavi Motlagh ,&nbsp;Ali Moghadas Jafari ,&nbsp;Amin Ghorbani ,&nbsp;Amir Dehghanpour ,&nbsp;Noushin Nabavi ,&nbsp;Shing Cheng Tan ,&nbsp;Mohsen Rashidi ,&nbsp;Afshin Taheriazam ,&nbsp;Maliheh Entezari ,&nbsp;Mohammad Ali Sheikh Beig Goharrizi","doi":"10.1016/j.biocel.2024.106566","DOIUrl":"10.1016/j.biocel.2024.106566","url":null,"abstract":"<div><p>Hepatocellular carcinoma (HCC), a significant challenge for public healthcare systems in developed Western countries including the USA, Canada, and the UK, is influenced by different risk factors including hepatitis virus infections, alcoholism, and smoking. The disruption in the balance of microRNAs (miRNAs) plays a vital function in tumorigenesis, given their function as regulators in numerous signaling networks. These miRNAs, which are mature and active in the cytoplasm, work by reducing the expression of target genes through their impact on mRNAs. MiRNAs are particularly significant in HCC as they regulate key aspects of the tumor, like proliferation and invasion. Additionally, during treatment phases such as chemotherapy and radiotherapy, the levels of miRNAs are key determinants. Pre-clinical experiments have demonstrated that altered miRNA expression contributes to HCC development, metastasis, drug resistance, and radio-resistance, highlighting related molecular pathways and processes like MMPs, EMT, apoptosis, and autophagy. Furthermore, the regulatory role of miRNAs in HCC extends beyond their immediate function, as they are also influenced by other epigenetic factors like lncRNAs and circular RNAs (circRNAs), as discussed in recent reviews. Applying these discoveries in predicting the prognosis of HCC could mark a significant advancement in the therapy of this disease.</p></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"170 ","pages":"Article 106566"},"PeriodicalIF":4.0,"publicationDate":"2024-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140186232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"YAP upregulates AMPKα1 to induce cancer cell senescence","authors":"Yongtong Zhan ,&nbsp;Guihao Wu ,&nbsp;Xuhong Fan ,&nbsp;Ze Fu ,&nbsp;Yue Ni ,&nbsp;Beini Sun ,&nbsp;Hongce Chen ,&nbsp;Tongsheng Chen ,&nbsp;Xiaoping Wang","doi":"10.1016/j.biocel.2024.106559","DOIUrl":"10.1016/j.biocel.2024.106559","url":null,"abstract":"<div><p>Yes-associated protein (YAP)—a major effector protein of the Hippo pathway— regulates cell proliferation, differentiation, apoptosis, and senescence. Amp-activated protein kinase (AMPK) is a key sensor that monitors cellular nutrient supply and energy status. Although YAP and AMPK are considered to regulate cellular senescence, it is still unclear whether AMPK is involved in YAP-regulated cellular senescence. Here, we found that YAP promoted AMPKα1 aggregation and localization around mitochondria by co-transfecting CFP-YAP and YFP-AMPKα1 plasmids. Subsequent live cell fluorescence resonance energy transfer (FRET) assay did not exhibit direct interaction between YAP and AMPKα1. FRET, Co-immunoprecipitation, and western blot experiments revealed that YAP directly bound to TEAD, enhancing the expression of AMPKα1 and p-AMPKα. Treatment with verteporfin inhibited YAP’s binding to TEAD and reversed the elevated expression of AMPKα1 in the cells overexpressing CFP-YAP. Verteporfin also reduced the proportion of AMPKα1 puncta in the cells co-expressing CFP-YAP and YFP-AMPKα1. In addition, the AMPKα1 puncta were demonstrated to inhibit cell viability, autophagy, and proliferation, and ultimately promote cell senescence. In conclusion, YAP binds to TEAD to upregulate AMPKα1 and promotes the formation of AMPKα1 puncta around mitochondria under the condition of co-expression of CFP-YAP and YFP-AMPKα1, in which AMPKα1 puncta lead to cellular senescence.</p></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"170 ","pages":"Article 106559"},"PeriodicalIF":4.0,"publicationDate":"2024-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140159386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A global phosphosite-correlated network map of Thousand And One Kinase 1 (TAOK1)","authors":"Pahal Priyanka ,&nbsp;Athira Perunelly Gopalakrishnan ,&nbsp;Mahammad Nisar ,&nbsp;Prathik Basthikoppa Shivamurthy ,&nbsp;Mejo George ,&nbsp;Levin John ,&nbsp;Diya Sanjeev ,&nbsp;Tanuja Yandigeri ,&nbsp;Sonet D. Thomas ,&nbsp;Ahmad Rafi ,&nbsp;Shobha Dagamajalu ,&nbsp;Anoop Kumar G. Velikkakath ,&nbsp;Chandran S. Abhinand ,&nbsp;Saptami Kanekar ,&nbsp;Thottethodi Subrahmanya Keshava Prasad ,&nbsp;Rex Devasahayam Arokia Balaya ,&nbsp;Rajesh Raju","doi":"10.1016/j.biocel.2024.106558","DOIUrl":"10.1016/j.biocel.2024.106558","url":null,"abstract":"<div><p>Thousand and one amino acid kinase 1 (TAOK1) is a sterile 20 family Serine/Threonine kinase linked to microtubule dynamics, checkpoint signaling, DNA damage response, and neurological functions. Molecular-level alterations of TAOK1 have been associated with neurodevelopment disorders and cancers. Despite their known involvement in physiological and pathophysiological processes, and as a core member of the hippo signaling pathway, the phosphoregulatory network of TAOK1 has not been visualized. Aimed to explore this network, we first analyzed the predominantly detected and differentially regulated TAOK1 phosphosites in global phosphoproteome datasets across diverse experimental conditions. Based on 709 qualitative and 210 quantitative differential cellular phosphoproteome datasets that were systematically assembled, we identified that phosphorylation at Ser421, Ser9, Ser965, and Ser445 predominantly represented TAOK1 in almost 75% of these datasets. Surprisingly, the functional role of all these phosphosites in TAOK1 remains unexplored. Hence, we employed a robust strategy to extract the phosphosites in proteins that significantly correlated in expression with predominant TAOK1 phosphosites. This led to the first categorization of the phosphosites including those in the currently known and predicted interactors, kinases, and substrates, that positively/negatively correlated with the expression status of each predominant TAOK1 phosphosites. Subsequently, we also analyzed the phosphosites in core proteins of the hippo signaling pathway. Based on the TAOK1 phosphoregulatory network analysis, we inferred the potential role of the predominant TAOK1 phosphosites. Especially, we propose pSer9 as an autophosphorylation and TAOK1 kinase activity-associated phosphosite and pS421, the most frequently detected phosphosite in TAOK1, as a significant regulatory phosphosite involved in the maintenance of genome integrity. Considering that the impact of all phosphosites that predominantly represent each kinase is essential for the efficient interpretation of global phosphoproteome datasets, we believe that the approach undertaken in this study is suitable to be extended to other kinases for accelerated research.</p></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"170 ","pages":"Article 106558"},"PeriodicalIF":4.0,"publicationDate":"2024-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140121294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Naringenin nanoparticles targeting cyclin B1 suppress the progression of rheumatoid arthritis-associated lung cancer by inhibiting fibroblast-to-myofibroblast transition","authors":"Xilong Wang ,&nbsp;Xiaoyu Zhang ,&nbsp;Zhipu Liu ,&nbsp;Na Zhao ,&nbsp;Xiaohan Li ,&nbsp;Peng Su ,&nbsp;Guixi Zheng ,&nbsp;Xin Zhang ,&nbsp;Hongxing Wang ,&nbsp;Yi Zhang","doi":"10.1016/j.biocel.2024.106557","DOIUrl":"10.1016/j.biocel.2024.106557","url":null,"abstract":"<div><p>There is growing evidence of an elevated risk of lung cancer in patients with rheumatoid arthritis. The poor prognosis of rheumatoid arthritis-associated lung cancer and the lack of therapeutic options pose an even greater challenge to the clinical management of patients. This study aimed to identify potential molecular targets associated with the progression of rheumatoid arthritis-associated lung cancer and examine the efficacy of naringenin nanoparticles targeting cyclin B1. Mendelian randomizatio analysis revealed that rheumatoid arthritis has a positive correlation with the risk of lung cancer. Cyclin B1 was significantly upregulated in patients with rheumatoid arthritis-associated lung cancer and was significantly overexpressed in synovial tissue fibroblasts. Furthermore, the overexpression of cyclin B1 in rheumatoid arthritis fibroblast-like synoviocytes, which promotes their proliferation and fibroblast-to-myofibroblast transition, can significantly contribute to the growth and infiltration of lung cancer cells. Importantly, our prepared naringenin nanoparticles targeting cyclin B1 effectively attenuated proliferation and fibroblast-to-myofibroblast transition by blocking cells at the G2/M phase. In vivo experiments, naringenin nanoparticles targeting cyclin B1 significantly alleviated the development of collagen-induced arthritis and lung orthotopic tumors. Collectively, our results reveal that naringenin nanoparticles targeting cyclin B1 can suppress the progression of rheumatoid arthritis-associated lung cancer by inhibiting fibroblast-to-myofibroblast transition. These findings provide new insights into the treatment of rheumatoid arthritis-associated lung cancer therapy.</p></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"169 ","pages":"Article 106557"},"PeriodicalIF":4.0,"publicationDate":"2024-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140068910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An update on the cell-free DNA-derived methylome as a non-invasive biomarker for coronary artery disease","authors":"Manoswini Dash ,&nbsp;Bhawna Mahajan ,&nbsp;Ghulam Mehdi Dar ,&nbsp;Parameswar Sahu ,&nbsp;Sundeep Singh Saluja","doi":"10.1016/j.biocel.2024.106555","DOIUrl":"10.1016/j.biocel.2024.106555","url":null,"abstract":"<div><p>Cardiovascular diseases are the foremost contributor to global mortality, presenting a complex etiology and an expanding array of risk factors. Coronary artery disease characterized by atherosclerotic plaque build-up in the coronary arteries, imposes significant mortality and financial burdens, especially in low- and middle-income nations. The pathogenesis of coronary artery disease involves a multifaceted interplay of genetic, environmental, and epigenetic factors. Epigenetic regulation contributes to the dynamic control of gene expression without altering the underlying DNA sequence. The mounting evidence that highlights the pivotal role of epigenetic regulation in coronary artery disease development and progression, offering potential avenues for the development of novel diagnostic biomarkers and therapeutic targets. Abnormal DNA methylation patterns are linked to the modulation of gene expression involved in crucial processes like lipid metabolism, inflammation, and vascular function in the context of coronary artery disease. Cell-free DNA has become invaluable in tumor biology as a liquid biopsy, while its applications in coronary artery disease are limited, but intriguing. Atherosclerotic plaque rupture causes myocardial infarction, by depriving heart muscles of oxygen, releasing cell-free DNA from dead cardiac cells, and providing a minimally invasive source to explore tissue-specific epigenetic alterations. We discussed the methodologies for studying the global methylome and hydroxy-methylome landscape, their advantages, and limitations. It explores methylome alterations in coronary artery disease, considering risk factors and their relevance in coronary artery disease genesis. The review also details the implications of MI-derived cell-free DNA for developing minimally invasive biomarkers and associated challenges.</p></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"169 ","pages":"Article 106555"},"PeriodicalIF":4.0,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140013591","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}