Journal of cellular biochemistry最新文献

{"title":"Orexin-A Inhibits Lipopolysaccharide-Induced Cell Migration in Cultured Mouse Astrocytes via Activation of Orexin 1 Receptor: Involvement of GABA Signaling","authors":"Hyunjin Shin,&nbsp;Sheu-Ran Choi,&nbsp;Dong-Wook Kang,&nbsp;Hyeryeong Lee,&nbsp;Jaehong Park,&nbsp;Miae Lee,&nbsp;Miok Bae,&nbsp;Yeonhee Ryu,&nbsp;Suk-Yun Kang,&nbsp;Chang Woo Chae,&nbsp;Hyun-Woo Kim","doi":"10.1002/jcb.70089","DOIUrl":"10.1002/jcb.70089","url":null,"abstract":"<p>It has been suggested that orexin-A (OXA) exerts neuroprotective and anti-inflammatory effects in the nervous system, while there is limited understanding of the role of OXA in cortical astrocytes under inflammation. This study was designed to investigate whether OXA could inhibit astrocyte migration induced by lipopolysaccharide (LPS) treatment and whether this action of OXA is mediated by activation of orexin 1 receptor (OX1R) in cultured mouse cortical astrocytes. OXA and OX1R were expressed in glial fibrillary acidic protein (GFAP)-positive cultured mouse astrocytes, and their expression was significantly increased by lipopolysaccharide (LPS) treatment. In addition, treatment of LPS induced significant increases in not only astrocyte migration but also phosphorylation of K + -Cl- cotransporter 2 (KCC2), ERK, and p38 MAPK, and these increases were inhibited by OXA treatment. This inhibitory effect of OXA was restored by treatment of the OX1R antagonist, SB334867. Furthermore, OXA treatment increased GABA immunoreactivity in LPS-treated cultured astrocytes and restored the expression of the GABA transporters GAT1 and GAT3 to levels comparable to those of the control group. This effect was abolished by SB334867 treatment. Collectively, these results suggest that OXA inhibits LPS-induced abnormal astrocyte migration via direct activation of orexin 1 receptor and that this inhibitory effect may be related to the modulation of intracellular GABA levels and GAT expression as well as dephosphorylation of KCC2, ERK, and p38 MAPK.</p>","PeriodicalId":15219,"journal":{"name":"Journal of cellular biochemistry","volume":"127 4","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13063212/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147638540","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":"Hyperglycemia Leads to BMSC Impaired Osteogenesis, Enhanced Adipogenesis, and Altered Metabolism.","authors":"Suzanna Shirazi, Ezaldeen Esawi, Zeyad D Nassar, Stan Gronthos, Dimitrios Cakouros","doi":"10.1002/jcb.70090","DOIUrl":"https://doi.org/10.1002/jcb.70090","url":null,"abstract":"<p><p>Diabetes is a major risk factor for osteoporosis, which negatively impacts bone health, but the mechanisms underlying the effects of hyperglycemia on bone marrow mesenchymal/stromal cells (BMSC) are not fully understood. This study investigated how high glucose levels influence BMSC differentiation, proliferation, viability, and metabolism. The results demonstrated that high glucose inhibits osteogenesis in human BMSC, as evidenced by reduced alkaline phosphatase activity, impaired calcium deposition, and downregulation of key osteogenic genes (RUNX2, ALP). Conversely, high glucose conditions promoted adipogenesis, characterized by increased percentage of cells with lipid droplets, and upregulation of adipogenic genes (PPARγ2, CEBPα, AdipoQ), suggesting a shift towards fat cell differentiation. Furthermore, BMSC cultured in high glucose showed decreased proliferation, elevated DNA damage, increased oxidative stress, enhanced apoptosis and senescence, particularly in later passages, highlighting the negative impact of hyperglycemia on BMSC viability. Metabolomic profiling of osteogenic and adipogenic differentiation in normal and high glucose conditions revealed key metabolic shifts, with nicotinamide adenine dinucleotide (NAD+) and l-glutamate/α-ketoglutarate (α-KG) identified as critical metabolites driving these processes. Supplementation with NAD+ and α-KG in high glucose conditions significantly enhanced ALP activity. These findings suggest that high glucose promotes adipogenesis at the expense of osteogenesis, exacerbating cellular damage and accelerating aging in BMSC. The identification of NAD+ and α-KG as key regulators in this process provides new insights into the metabolic mechanisms behind impaired bone health in diabetes and highlights potential therapeutic avenues to counteract these detrimental effects to better manage diabetes-related bone diseases.</p>","PeriodicalId":15219,"journal":{"name":"Journal of cellular biochemistry","volume":"127 4","pages":"e70090"},"PeriodicalIF":2.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13109826/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147772506","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":"EXPRESSION OF CONCERN: Collaboration of Myc and RUNX2 in Lymphoma Simulates T-Cell Receptor Signaling and Attenuates p53 Pathway Activity","authors":"","doi":"10.1002/jcb.70087","DOIUrl":"10.1002/jcb.70087","url":null,"abstract":"<p><b>EXPRESSION OF CONCERN</b>: J. Hay, K. Gilroy, C. Huser, A. Kilbey, A. Mcdonald, A. MacCallum, A. Holroyd, E. Cameron, and J. C. Neil, “Collaboration of MYC and RUNX2 in Lymphoma Simulates T-Cell Receptor Signaling and Attenuates p53 Pathway Activity,” <i>Journal of Cellular Biochemistry</i> 120, no. 10 (2019): 18332–18345, https://doi.org/10.1002/jcb.29143.</p><p>This Expression of Concern is for the above article, published online on 30 June 2019 in Wiley Online Library (wileyonlinelibrary.com), and has been issued by agreement between the journal Editor-in-Chief, Christian Behl; and Wiley Periodicals LLC. The Expression of Concern has been agreed upon following concerns raised by a third-party regarding image duplication. An investigation confirmed that the WT and +RUNX1 images in Figure 5A had been previously published in another article by some of the same authors. In each article, the duplicated images were used to represent fibroblasts from different species. The authors cooperated with the investigation and stated that the duplication occurred inadvertently. They also provided some supporting data. The authors' institution confirmed that the overall conclusions of the article remain valid. The journal has decided to issue an Expression of Concern to inform and alert readers of the misrepresentation of images in the article.</p>","PeriodicalId":15219,"journal":{"name":"Journal of cellular biochemistry","volume":"127 3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcb.70087","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147512066","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":"RETRACTION: Combined Supplementation of Vanadium and Fish Oil Suppresses Tumor Growth, Cell Proliferation, and Induces Apoptosis in DMBA-Induced Rat Mammary Carcinogenesis","authors":"","doi":"10.1002/jcb.70083","DOIUrl":"10.1002/jcb.70083","url":null,"abstract":"<p><b>RETRACTION:</b> S. Manna, S. Das, M. Chatterjee, M. Janarthan, and M. Chatterjee, <i>Journal of Cellular Biochemistry</i> 112, no. 9 (2011): 2327-2339, https://doi.org/10.1002/jcb.23153.</p><p>The above article, published online on 18 April 2011 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Christian Behl; and Wiley Periodicals LLC. The retraction has been agreed upon following concerns raised by a third-party regarding image duplication. An investigation confirmed overlaps among the immunohistochemistry micrographs presented in Figures 4A-4D. Each image was intended to represent a different sample and treatment. The authors failed to provide a satisfactory explanation or any supporting data. The editors consider the results and conclusions unreliable. The authors disagree with the retraction.</p>","PeriodicalId":15219,"journal":{"name":"Journal of cellular biochemistry","volume":"127 3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcb.70083","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147486121","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":"RETRACTION: Long Noncoding RNA lnc-ABCA12-3 Promotes Cell Migration, Invasion, and Proliferation by Regulating Fibronectin 1 in Esophageal Squamous Cell Carcinoma","authors":"","doi":"10.1002/jcb.70081","DOIUrl":"https://doi.org/10.1002/jcb.70081","url":null,"abstract":"<p><b>RETRACTION:</b> J. Ma, Y. Xiao, B. Tian, S. Chen, B. Zhang, J. Wu, Z. Wu, X. Li, J. Tang, D. Yang, Y. Zhou, H. Wang, M. Su, and W. Wang, “Long Noncoding RNA lnc-ABCA12-3 Promotes Cell Migration, Invasion, and Proliferation by Regulating Fibronectin 1 in Esophageal Squamous Cell Carcinoma,” <i>Journal of Cellular Biochemistry</i> 121, no. 2 (2020): 1374–1387, https://doi.org/10.1002/jcb.29373.</p><p>The above article, published online on 12 September 2019 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the authors; the journal Editor-in-Chief, Christian Behl; and Wiley Periodicals LLC. The retraction has been agreed due to concerns raised by third parties. Specifically, several instances of image duplication within and across Figures 3B and 7 C have been detected. The clarification and materials provided by the authors upon request did not address the concerns. Accordingly, the article is retracted as the editors have lost confidence in the integrity and accuracy of the whole body of data presented in the article and consider its conclusions invalid.</p>","PeriodicalId":15219,"journal":{"name":"Journal of cellular biochemistry","volume":"127 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcb.70081","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146139435","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":"New Insights Into the Role of Polo-Like Kinase 3 in Lung Tumorigenesis","authors":"Cen Li,&nbsp;Arko Samad,&nbsp;Casey Ostrowski,&nbsp;S. M. Shafiqul Alam,&nbsp;Changhong Yin,&nbsp;Selvaraj Ayyamperumal,&nbsp;Jinjin Chen,&nbsp;Minghao Zhong,&nbsp;Weihua Huang,&nbsp;Yinsheng Wang,&nbsp;Humayun K. Islam,&nbsp;John L. Phillips,&nbsp;Marietta Y. W. T. Lee,&nbsp;Dazhong Xu","doi":"10.1002/jcb.70084","DOIUrl":"10.1002/jcb.70084","url":null,"abstract":"<div>\u0000 \u0000 <p>Polo-like kinase 3 (PLK3) plays major roles in cell cycle regulation, DNA repair, and cellular responses to hypoxia. Our prior studies demonstrated that PLK3 negatively regulates the hypoxic response by directly phosphorylating and destabilizing HIF-1α and by destabilizing the E3 ubiquitin ligase SIAH2. We also find that PLK3 stabilizes PTEN by direct phosphorylation. <i>Plk3</i> knockout mice exhibit increased spontaneous tumorigenesis in multiple organs, particularly the lung, at an advanced age. Tumors from these mice tend to be highly vascularized, consistent with the function of PLK3 in the hypoxic response. However, another study only observed increased tumorigenesis in female <i>Plk3</i> knockout mice. The present study further explored the role of PLK3 in lung tumorigenesis. We find that PLK3 can phosphorylate SIAH2 in vitro, confirming our hypothesis that PLK3 regulates SIAH2 by direct phosphorylation. We detected a negative correlation between the levels of PLK3 and SIAH2 and a positive correlation between HIF-1α and SIAH2 in both human lung adenocarcinoma and squamous cell carcinoma. We observed an increase in lung tumorigenesis in <i>Plk3</i> knockout mice in the A/J strain background. Our RNA-Seq analysis revealed significantly increased expression of genes involved in oncogenic pathways and the immune response in lung tumors from <i>Plk3</i> knockout mice. Finally, we find that induced systemic SIAH2 expression promotes CD8 T cell infiltration into subcutaneous tumors in a syngeneic mouse model. Our work further supports the tumor suppressive role of PLK3 in lung cancer and discovered a novel involvement of PLK3 in the regulation of the immune microenvironment of lung tumors.</p>\u0000 </div>","PeriodicalId":15219,"journal":{"name":"Journal of cellular biochemistry","volume":"127 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146119098","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":"Structural and Functional Insights Into Lyn Kinase: From Immune Regulation to Therapeutic Targeting","authors":"Alisha Khan,&nbsp;Aaliya Taiyab,&nbsp;Gulam Mustafa Hasan,&nbsp;Saima Wajid,&nbsp;Md. Imtaiyaz Hassan","doi":"10.1002/jcb.70082","DOIUrl":"10.1002/jcb.70082","url":null,"abstract":"<div>\u0000 \u0000 <p>Lyn kinase, a member of the Src family of kinases, is a critical regulator of immune cell signaling, regulating key processes including activation, proliferation, survival, and apoptosis. Dysregulated Lyn kinase activity causes haematological malignancies, autoimmune disorders, solid tumors, neurodegenerative, cardiovascular, and metabolic disorders. Here, we aimed to provide a comprehensive account of Lyn kinase biology, highlighting its structural features, regulatory roles in immune and cellular signaling, and pathological implications across diseases, including cancers, neurodegenerative disorders, autoimmune diseases, and metabolic disorders. We further examined emerging therapeutic strategies, including small-molecule inhibitors, monoclonal antibodies, and natural compounds, and highlighted the therapeutic potential of Lyn kinase as a promising drug target. Overexpression of Lyn contributes to tumor growth, metastasis, and resistance to treatment in leukaemia, prostate, breast, lung, and pancreatic cancers. Beyond oncology, emerging evidence links Lyn kinase to neuroinflammation, synaptic dysfunction, and metabolic regulation, further underscoring its broad disease relevance. Lyn kinase is considered a viable therapeutic target, with ongoing research focusing on small-molecule inhibitors, monoclonal antibodies, and natural compounds like flavonoids and polyphenols that have exhibited promising preclinical and clinical outcomes. We summarized current insights into Lyn kinase biology, highlighting its pathological significance and discussing therapeutic opportunities arising from the modulation of this enzyme.</p>\u0000 </div>","PeriodicalId":15219,"journal":{"name":"Journal of cellular biochemistry","volume":"127 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146052206","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":"HEPES in Cell Culture Alters the Multi-Omics Profile Exhibited by Gaucher Disease Fibroblasts","authors":"Eleonore M. Corazolla,&nbsp;Bauke V. Schomakers,&nbsp;Maria M. Trętowicz,&nbsp;Jill Hermans,&nbsp;Michel van Weeghel,&nbsp;Frédéric M. Vaz,&nbsp;Mia L. Pras-Raves,&nbsp;Karen Ghauharali-van der Vlugt,&nbsp;Femke S. Beers-Stet,&nbsp;Susanna M. I. Goorden,&nbsp;Judith Jansen-Meijer,&nbsp;Georges E. Janssens,&nbsp;Carla E. M. Hollak,&nbsp;Riekelt H. Houtkooper,&nbsp;André B. P. van Kuilenburg","doi":"10.1002/jcb.70080","DOIUrl":"10.1002/jcb.70080","url":null,"abstract":"<p>Lysosomal function can be affected by components in cell culture. This in turn may influence cellular metabolism and, consequently, research and diagnostics outcomes. One such component is the commonly used pH buffer 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES). HEPES specifically impacts the trafficking of the lysosomal enzyme glucocerebrosidase, which is deficient in Gaucher disease (GD). Understanding how HEPES affects cellular models of GD is essential, since glucocerebrosidase is central to diagnostic testing and the investigation of GD pathophysiology. Therefore, we examined the broader effects of HEPES on cultured fibroblasts from individuals with GD and healthy controls. We cultured dermal fibroblasts of eight adults with GD and seven healthy age- and sex-matched controls. The cells were cultured in two culture media, Ham's F10 and DMEM, both with and without HEPES. We assessed glucocerebrosidase enzyme activity and sphingolipid concentrations using a quantitative UPLC-MS/MS method. Additionally, we conducted multi-omics analyses, consisting of lipidomics, metabolomics and proteomics, to explore the broader impact of HEPES in cell culture on fibroblasts. Glucocerebrosidase activity in cell lysates increased after HEPES exposure in both GD and control fibroblasts, to an extent that may influence diagnostic outcomes. In GD fibroblasts, substrate accumulation was absent and not altered by HEPES exposure. GD fibroblasts exhibited a multi-omics profile largely overlapping with healthy controls and lacking the typical pathological features associated with GD in other cell types, such as mitochondrial dysfunction, dysregulated autophagy, disruption of intracellular calcium homeostasis, ER stress and chronic oxidative stress. In addition, the multi-omics profile was altered by HEPES, however in a non-specific manner. In conclusion, HEPES influences fibroblasts in culture, both from healthy controls and from patients with GD. Furthermore, GD fibroblasts lack a specific disease-related profile. This renders cultured fibroblasts unsuitable for studying pathophysiological processes in GD. Culturing GD fibroblasts with HEPES may compromise the reliability of diagnostics.</p>","PeriodicalId":15219,"journal":{"name":"Journal of cellular biochemistry","volume":"127 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12809196/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145989248","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":"SPI1 Regulates Autophagy by Promoting ATG7 Transcription to Enhance Ferroptosis in Myocardial Ischemia/Reperfusion Injury","authors":"Wu-lin Li,&nbsp;Xiao Han,&nbsp;Wei-long Pan,&nbsp;Hui Wang,&nbsp;Da-li You,&nbsp;Xian-ting Chen,&nbsp;Xiao Wu,&nbsp;Ming-ming Jin,&nbsp;Fei Wang","doi":"10.1002/jcb.70078","DOIUrl":"https://doi.org/10.1002/jcb.70078","url":null,"abstract":"<div>\u0000 \u0000 <p>Myocardial ischemia/reperfusion injury (MIRI) commonly arises during medical procedures for coronary artery disease (CAD), a global health issue. Inhibiting autophagy-dependent ferroptosis has emerged as an effective strategy for MIRI treatment, yet its precise mechanisms warrant further exploration. A murine model of myocardial ischemia/reperfusion (I/R) was employed, and cardiac myocytes were subjected to hypoxia/reoxygenation (H/R). Myocardial tissue alterations were assessed using Evans blue/TTC staining, HE staining, and TUNEL assays. An automated biochemical analyzer was used to quantify serum creatine kinase (CK) and lactate dehydrogenase (LDH) levels. Myocardial cell viability was evaluated using Cell Counting Kit-8 (CCK-8) assays. The interaction of the ATG7 promoter with SPI1 was explored through ChIP experiments. The expression levels of autophagy markers (Beclin-1, LC3The expr, ATG7, and SPI1 were assessed via immunohistochemistry, immunofluorescence, quantitative real-time polymerase chain reaction (qRT-PCR), and western blot analysis. Various indicators, including LDH, ROS, MDA, Fe2 + , GSH, GPx4, and FTH1, were measured to characterize the ferroptosis process. In MIRI model mice, autophagy-dependent ferroptosis clearly occurred, and ATG7 expression was elevated. ATG7 knockdown effectively alleviated MIRI and inhibited autophagy-induced ferroptosis. SPI1 was identified as a key regulator in this process. SPI1 bound to the ATG7 promoter region, enhancing ATG7 transcription during myocardial I/R and thereby modulating both ferroptosis and autophagy. SPI1 knockdown inhibited ferroptosis and alleviated MIRI by suppressing autophagy. The results of our study revealed that SPI1 promoted ATG7 transcription, exacerbating ferroptosis in MIRI. These findings suggest that therapeutic strategies targeting ferroptosis and autophagy may mitigate cardiovascular diseases in MIRI.</p></div>","PeriodicalId":15219,"journal":{"name":"Journal of cellular biochemistry","volume":"126 12","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145699097","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":"Integrative Multi-Omics Analysis Unveils the Molecular Mechanisms by Which TP53 Mutation Influence Early Decitabine Resistance in Myelodysplastic Syndrome","authors":"Wei Chen,&nbsp;Xiaojing Ge,&nbsp;Hailing Xu,&nbsp;Tong Yang,&nbsp;Xiuying Wu,&nbsp;Jinting An,&nbsp;Yuye Ren,&nbsp;Lan Zhang","doi":"10.1002/jcb.70076","DOIUrl":"https://doi.org/10.1002/jcb.70076","url":null,"abstract":"<div>\u0000 \u0000 <p>The myelodysplastic syndrome (MDS) is group of clonal hematopoietic stem cell disorders typified by peripheral cytopenia, dysplastic hematopoietic progenitors, a hypercellular or hypocellular bone marrow, and a high risk of conversion to acute myeloid leukemia. TP53 is a tumor suppressor gene that plays an important role in tumor suppression. Decitabine (DAC) monotherapy has been shown to improve the response rates in TP53-mutated MDS, while the molecular mechanisms of clinical responses are unclear. This study aimed to initially evaluate the TP53 gene locus mutation and the regulation mechanism of DAC on gene expression in AML-MDS cell lines. We detected the mutation of TP53 gene locus in three myeloid tumor cell lines, SKM-1 (mutTP53), M-07e (wtTP53) and HL60 (nullTP53). Then, we performed transcriptomic and proteomic and methylation data in M-07e (wtTP53) and SKM-1 (mutTP53) cells and screened out LGALS1, which is a poor prognostic indicator, as the potential target of TP53 by comparing analysis. We uncovered 31 potential key genes showing differential early responses to DAC treatment in TP53-mutant versus wild-type cells, which may be associated with resistance development. This study revealed the potential molecular mechanisms of TP53 gene locus mutation in DAC-treated MDS.</p>\u0000 </div>","PeriodicalId":15219,"journal":{"name":"Journal of cellular biochemistry","volume":"126 12","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145699177","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}