Molecular and Cellular Biology最新文献_第5页

Inflammatory Mediators Suppress FGFR2 Expression in Human Keratinocytes to Promote Inflammation. 炎症介质抑制人角质形成细胞中表皮生长因子受体 2 的表达，从而促进炎症。

IF 3.2 2区生物学

Molecular and Cellular Biology Pub Date : 2024-01-01 Epub Date: 2024-09-28 DOI: 10.1080/10985549.2024.2399766

Luca Ferrarese, Michael Koch, Artemis Baumann, Liliana Bento-Lopes, Daria Wüst, Ivan Berest, Manfred Kopf, Sabine Werner

{"title":"Inflammatory Mediators Suppress FGFR2 Expression in Human Keratinocytes to Promote Inflammation.","authors":"Luca Ferrarese, Michael Koch, Artemis Baumann, Liliana Bento-Lopes, Daria Wüst, Ivan Berest, Manfred Kopf, Sabine Werner","doi":"10.1080/10985549.2024.2399766","DOIUrl":"10.1080/10985549.2024.2399766","url":null,"abstract":"Fibroblast growth factors (FGFs) are key orchestrators of development, tissue homeostasis and repair. FGF receptor (FGFR) deficiency in mouse keratinocytes causes an inflammatory skin phenotype with similarities to atopic dermatitis, but the human relevance is unclear. Therefore, we generated human keratinocytes with a CRISPR/Cas9-induced knockout of FGFR2. Loss of this receptor promoted the expression of interferon-stimulated genes and pro-inflammatory cytokines under homeostatic conditions and in particular in response to different inflammatory mediators. Expression of FGFR2 itself was strongly downregulated in cultured human keratinocytes exposed to various pro-inflammatory stimuli. This is relevant in vivo, because bioinformatics analysis of bulk and single-cell RNA-seq data showed strongly reduced expression of FGFR2 in lesional skin of atopic dermatitis patients, which likely aggravates the inflammatory phenotype. These results reveal a key function of FGFR2 in human keratinocytes in the suppression of inflammation and suggest a role of FGFR2 downregulation in the pathogenesis of atopic dermatitis and possibly other inflammatory diseases.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"489-504"},"PeriodicalIF":3.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11529413/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142350049","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}

引用次数: 0

Contribution of CENP-F to FOXM1-Mediated Discordant Centromere and Kinetochore Transcriptional Regulation. CENP-F 对 FOXM1 介导的不和谐中心粒和动点转录调节的贡献

IF 3.2 2区生物学

Molecular and Cellular Biology Pub Date : 2024-01-01 Epub Date: 2024-05-23 DOI: 10.1080/10985549.2024.2350543

Sakshi Khurana, Dileep Varma, Daniel R Foltz

{"title":"Contribution of CENP-F to FOXM1-Mediated Discordant Centromere and Kinetochore Transcriptional Regulation.","authors":"Sakshi Khurana, Dileep Varma, Daniel R Foltz","doi":"10.1080/10985549.2024.2350543","DOIUrl":"10.1080/10985549.2024.2350543","url":null,"abstract":"Proper chromosome segregation is required to ensure chromosomal stability. The centromere (CEN) is a unique chromatin domain defined by CENP-A and is responsible for recruiting the kinetochore (KT) during mitosis, ultimately regulating microtubule spindle attachment and mitotic checkpoint function. Upregulation of many CEN/KT genes is commonly observed in cancer. Here, we show that although FOXM1 occupies promoters of many CEN/KT genes with MYBL2, FOXM1 overexpression alone is insufficient to drive the FOXM1-correlated transcriptional program. CENP-F is canonically an outer kinetochore component; however, it functions with FOXM1 to coregulate G2/M transcription and proper chromosome segregation. Loss of CENP-F results in altered chromatin accessibility at G2/M genes and reduced FOXM1-MBB complex formation. We show that coordinated CENP-FFOXM1 transcriptional regulation is a cancer-specific function. We observe a small subset of CEN/KT genes including CENP-C, that are not regulated by FOXM1. Upregulation of CENP-C in the context of CENP-A overexpression leads to increased chromosome missegregation and cell death suggesting that escape of CENP-C from FOXM1 regulation is a cancer survival mechanism. Together, we show that FOXM1 and CENP-F coordinately regulate G2/M genes, and this coordination is specific to a subset of genes to allow for maintenance of chromosome instability levels and subsequent cell survival.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"209-225"},"PeriodicalIF":3.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11204039/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141081916","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}

引用次数: 0

Regulation of T Cell Signaling and Immune Responses by PTPN22. PTPN22 对 T 细胞信号和免疫反应的调控

IF 3.2 2区生物学

Molecular and Cellular Biology Pub Date : 2024-01-01 Epub Date: 2024-07-22 DOI: 10.1080/10985549.2024.2378810

Rebecca J Brownlie, Robert J Salmond

引用次数: 0

The Deubiquitylase Otub1 Regulates the Chemotactic Response of Splenic B Cells by Modulating the Stability of the γ-Subunit Gng2. 去泛素化酶Otub1通过调节γ亚基Gng2的稳定性调控脾B细胞的趋化反应

IF 3.2 2区生物学

Molecular and Cellular Biology Pub Date : 2024-01-01 Epub Date: 2024-01-29 DOI: 10.1080/10985549.2023.2290434

Vincent M Luo, Connie Shen, Samantha Worme, Aanya Bhagrath, Estelle Simo-Cheyou, Steven Findlay, Steven Hébert, William Wai Lam Poon, Zahra Aryanpour, Thomas Zhang, René P Zahedi, Jonathan Boulais, Zachary S Buchwald, Christoph H Borchers, Jean-Francois Côté, Claudia L Kleinman, Judith N Mandl, Alexandre Orthwein

{"title":"The Deubiquitylase Otub1 Regulates the Chemotactic Response of Splenic B Cells by Modulating the Stability of the γ-Subunit Gng2.","authors":"Vincent M Luo, Connie Shen, Samantha Worme, Aanya Bhagrath, Estelle Simo-Cheyou, Steven Findlay, Steven Hébert, William Wai Lam Poon, Zahra Aryanpour, Thomas Zhang, René P Zahedi, Jonathan Boulais, Zachary S Buchwald, Christoph H Borchers, Jean-Francois Côté, Claudia L Kleinman, Judith N Mandl, Alexandre Orthwein","doi":"10.1080/10985549.2023.2290434","DOIUrl":"10.1080/10985549.2023.2290434","url":null,"abstract":"The ubiquitin proteasome system performs the covalent attachment of lysine 48-linked polyubiquitin chains to substrate proteins, thereby targeting them for degradation, while deubiquitylating enzymes (DUBs) reverse this process. This posttranslational modification regulates key features both of innate and adaptative immunity, including antigen presentation, protein homeostasis and signal transduction. Here we show that loss of one of the most highly expressed DUBs, Otub1, results in changes in murine splenic B cell subsets, leading to a significant increase in marginal zone and transitional B cells and a concomitant decrease in follicular B cells. We demonstrate that Otub1 interacts with the γ-subunit of the heterotrimeric G protein, Gng2, and modulates its ubiquitylation status, thereby controlling Gng2 stability. Proximal mapping of Gng2 revealed an enrichment in partners associated with chemokine signaling, actin cytoskeleton and cell migration. In line with these findings, we show that Otub1-deficient B cells exhibit greater Ca2+ mobilization, F-actin polymerization and chemotactic responsiveness to Cxcl12, Cxcl13 and S1P in vitro, which manifests in vivo as altered localization of B cells within the spleen. Together, our data establishes Otub1 as a novel regulator of G-protein coupled receptor signaling in B cells, regulating their differentiation and positioning in the spleen.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"1-16"},"PeriodicalIF":3.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10829841/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139546859","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}

引用次数: 0

Mutations at BCL11B Exon 4 Associated with T Cell Acute Lymphoblastic Leukemia Are Facilitated by AID and Formation of Non-B DNA Conformations. 与 T 细胞急性淋巴细胞白血病有关的 BCL11B 第 4 外显子突变由 AID 促进并形成非 B DNA 构型。

IF 3.2 2区生物学

Molecular and Cellular Biology Pub Date : 2024-01-01 Epub Date: 2024-11-07 DOI: 10.1080/10985549.2024.2419661

Urbi Roy, Anju Sharma, Shivangi Sharma, Sumedha Dahal, Nitu Kumari, Sagar Sanjiv Desai, Susmita Kumari, Jyotika Dixit, Arun Sharma M, Najma Nujoom, Bibha Choudhary, Sathees C Raghavan

{"title":"Mutations at BCL11B Exon 4 Associated with T Cell Acute Lymphoblastic Leukemia Are Facilitated by AID and Formation of Non-B DNA Conformations.","authors":"Urbi Roy, Anju Sharma, Shivangi Sharma, Sumedha Dahal, Nitu Kumari, Sagar Sanjiv Desai, Susmita Kumari, Jyotika Dixit, Arun Sharma M, Najma Nujoom, Bibha Choudhary, Sathees C Raghavan","doi":"10.1080/10985549.2024.2419661","DOIUrl":"10.1080/10985549.2024.2419661","url":null,"abstract":"One of the primary reasons behind the pathogenesis of T cell acute lymphoblastic leukemia (T-ALL) is the deregulation of the transcription factor BCL11B. The exon 4 of BCL11B harbors several driver mutations, which abolishes its DNA-binding ability. The high frequency of C > T or G > A conversion in close vicinity of AID (Activation-induced cytidine deaminase)-hotspot motifs in the deregulated gene prompted us to investigate the role of AID in BCL11B mutagenesis. Our results reveal that AID is expressed in T-ALL patient-derived cells, binds to BCL11B fragile region (FR) in exon 4 of T cells in vivo, and generates a signature mutation pattern in this region. The mutation frequency in BCL11B FR could be modulated upon overexpression of the AID gene in the knockout background, further suggesting the involvement of AID in BCL11B mutagenesis. Importantly, various lines of experimentation reveal that BCL11B FR could fold into parallel G-quadruplex, triplex, and hairpin structures, which could act as a replication/transcription block, causing mutagenesis. Thus, our results suggest that AID binds to BCL11B exon 4 due to non-B DNA formation, causing U:G mismatches or replication blocks, which, when repaired erroneously, generates deleterious mutations, resulting in loss of functionality of BCL11B, and thus becomes the cause of T-ALL.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"590-606"},"PeriodicalIF":3.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11583620/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604653","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}

引用次数: 0

Staufen1 Represses the FOXA1-Regulated Transcriptome by Destabilizing FOXA1 mRNA in Colorectal Cancer Cells. Staufen1 通过破坏结直肠癌细胞中 FOXA1 mRNA 的稳定性来抑制 FOXA1 调节的转录组。

IF 3.2 2区生物学

Molecular and Cellular Biology Pub Date : 2024-01-01 Epub Date: 2024-02-12 DOI: 10.1080/10985549.2024.2307574

Katherine R Pasterczyk, Xiao Ling Li, Ragini Singh, Meira S Zibitt, Corrine Corrina R Hartford, Lorinc Pongor, Lisa M Jenkins, Yue Hu, Patrick X Zhao, Bruna R Muys, Suresh Kumar, Nitin Roper, Mirit I Aladjem, Yves Pommier, Ioannis Grammatikakis, Ashish Lal

{"title":"Staufen1 Represses the FOXA1-Regulated Transcriptome by Destabilizing FOXA1 mRNA in Colorectal Cancer Cells.","authors":"Katherine R Pasterczyk, Xiao Ling Li, Ragini Singh, Meira S Zibitt, Corrine Corrina R Hartford, Lorinc Pongor, Lisa M Jenkins, Yue Hu, Patrick X Zhao, Bruna R Muys, Suresh Kumar, Nitin Roper, Mirit I Aladjem, Yves Pommier, Ioannis Grammatikakis, Ashish Lal","doi":"10.1080/10985549.2024.2307574","DOIUrl":"10.1080/10985549.2024.2307574","url":null,"abstract":"Transcription factors play key roles in development and disease by controlling gene expression. Forkhead box A1 (FOXA1), is a pioneer transcription factor essential for mouse development and functions as an oncogene in prostate and breast cancer. In colorectal cancer (CRC), FOXA1 is significantly downregulated and high FOXA1 expression is associated with better prognosis, suggesting potential tumor suppressive functions. We therefore investigated the regulation of FOXA1 expression in CRC, focusing on well-differentiated CRC cells, where FOXA1 is robustly expressed. Genome-wide RNA stability assays identified FOXA1 as an unstable mRNA in CRC cells. We validated FOXA1 mRNA instability in multiple CRC cell lines and in patient-derived CRC organoids, and found that the FOXA1 3'UTR confers instability to the FOXA1 transcript. RNA pulldowns and mass spectrometry identified Staufen1 (STAU1) as a potential regulator of FOXA1 mRNA. Indeed, STAU1 knockdown resulted in increased FOXA1 mRNA and protein expression due to increased FOXA1 mRNA stability. Consistent with these data, RNA-seq following STAU1 knockdown in CRC cells revealed that FOXA1 targets were upregulated upon STAU1 knockdown. Collectively, this study uncovers a molecular mechanism by which FOXA1 is regulated in CRC cells and provides insights into our understanding of the complex mechanisms of gene regulation in cancer.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"43-56"},"PeriodicalIF":3.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10950277/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139723241","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}

引用次数: 0

LncRNA AA465934 Improves Podocyte Injury by Promoting Tristetraprolin-Mediated HMGB1 DownRegulation in Diabetic Nephropathy. LncRNA AA465934通过促进Tristetraprolin介导的HMGB1下调改善糖尿病肾病的荚膜细胞损伤

IF 3.2 2区生物学

Molecular and Cellular Biology Pub Date : 2024-01-01 Epub Date: 2024-03-23 DOI: 10.1080/10985549.2024.2325527

Nan Yang, Yue Zhang, Peiyao Ren, Li Zhao, Danna Zheng, Lanjun Fu, Juan Jin

{"title":"LncRNA AA465934 Improves Podocyte Injury by Promoting Tristetraprolin-Mediated HMGB1 DownRegulation in Diabetic Nephropathy.","authors":"Nan Yang, Yue Zhang, Peiyao Ren, Li Zhao, Danna Zheng, Lanjun Fu, Juan Jin","doi":"10.1080/10985549.2024.2325527","DOIUrl":"10.1080/10985549.2024.2325527","url":null,"abstract":"Although LncRNA AA465934 expression is reduced in high glucose (HG)-treated podocytes, its role in HG-mediated podocyte injury and diabetic nephropathy (DN) remains unknown. Herein, we investigated the role of AA465934 in HG-mediated podocyte injury and DN using a spontaneous type II diabetic nephropathy (T2DN) model. The model was created by injecting AA465934 overexpressed adeno-associated virus (AAV) or control into mice. The levels of renal function, proteinuria, renal structural lesions, and podocyte apoptosis were then examined. Furthermore, AA465934 and autophagy levels, as well as tristetraprolin (TTP) and high mobility group box 1 (HMGB1) expression changes were detected. We also observed podocyte injury and the binding ability of TTP to E3 ligase proviral insertion in murine lymphomas 2 (PIM2), AA465934, or HMGB1. According to the results, AA465934 improved DN progression and podocyte damage in T2DN mice. In addition, AA465934 bound to TTP and inhibited its degradation by blocking TTP-PIM2 binding. Notably, TTP knock-down blocked the ameliorating effects of AA465934 and TTP bound HMGB1 mRNA, reducing its expression. Overexpression of HMGB1 inhibited the ability of AA465934 and TTP to improve podocyte injury. Furthermore, AA465934 bound TTP, inhibiting TTP-PIM2 binding, thereby suppressing TTP degradation, downregulating HMGB1, and reversing autophagy downregulation, ultimately alleviating HG-mediated podocyte injury and DN. Based on these findings, we deduced that the AA465934/TTP/HMGB1/autophagy axis could be a therapeutic avenue for managing podocyte injury and DN.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"87-102"},"PeriodicalIF":3.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10986766/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140194168","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}

引用次数: 0

SPRING is a Dedicated Licensing Factor for SREBP-Specific Activation by S1P. SPRING 是 S1P 激活 SREBP 的专用许可因子。

IF 3.2 2区生物学

Molecular and Cellular Biology Pub Date : 2024-01-01 Epub Date: 2024-05-15 DOI: 10.1080/10985549.2024.2348711

Sebastian Hendrix, Josephine M E Tan, Klevis Ndoj, Jenina Kingma, Masoud Valiloo, Lobke F Zijlstra, Roelof Ottenhoff, Nabil G Seidah, Anke Loregger, Daniel L Kober, Noam Zelcer

{"title":"SPRING is a Dedicated Licensing Factor for SREBP-Specific Activation by S1P.","authors":"Sebastian Hendrix, Josephine M E Tan, Klevis Ndoj, Jenina Kingma, Masoud Valiloo, Lobke F Zijlstra, Roelof Ottenhoff, Nabil G Seidah, Anke Loregger, Daniel L Kober, Noam Zelcer","doi":"10.1080/10985549.2024.2348711","DOIUrl":"10.1080/10985549.2024.2348711","url":null,"abstract":"SREBP transcription factors are central regulators of lipid metabolism. Their proteolytic activation requires ER to the Golgi translocation and subsequent cleavage by site-1-protease (S1P). Produced as a proprotein, S1P undergoes autocatalytic cleavage from its precursor S1PA to mature S1PC form. Here, we report that SPRING (previously C12ORF29) and S1P interact through their ectodomains, and that this facilitates the autocatalytic cleavage of S1PA into its mature S1PC form. Reciprocally, we identified a S1P recognition-motif in SPRING and demonstrate that S1P-mediated cleavage leads to secretion of the SPRING ectodomain in cells, and in liver-specific Spring knockout (LKO) mice transduced with AAV-mSpring. By reconstituting SPRING variants into SPRINGKO cells we show that the SPRING ectodomain supports proteolytic maturation of S1P and SREBP signaling, but that S1P-mediated SPRING cleavage is not essential for these processes. Absence of SPRING modestly diminishes proteolytic maturation of S1PA→C and trafficking of S1PC to the Golgi. However, despite reaching the Golgi in SPRINGKO cells, S1PC fails to rescue SREBP signaling. Remarkably, whereas SREBP signaling was severely attenuated in SPRINGKO cells and LKO mice, that of ATF6, another S1P substrate, was unaffected in these models. Collectively, our study positions SPRING as a dedicated licensing factor for SREBP-specific activation by S1P.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"123-137"},"PeriodicalIF":3.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11110692/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140922665","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}

引用次数: 0

Deactivation of the Unfolded Protein Response Aggravated Renal AA Amyloidosis in HSF1 Deficiency Mice. 解除折叠蛋白反应会加重 HSF1 缺乏小鼠的肾 AA 淀粉样变性。

IF 3.2 2区生物学

Molecular and Cellular Biology Pub Date : 2024-01-01 Epub Date: 2024-05-17 DOI: 10.1080/10985549.2024.2347937

Wei Liu, Shunjie Xia, Fang Yao, Jia Huo, Junqiao Qian, Xiaomeng Liu, Langning Bai, Yu Song, Jinze Qian

{"title":"Deactivation of the Unfolded Protein Response Aggravated Renal AA Amyloidosis in HSF1 Deficiency Mice.","authors":"Wei Liu, Shunjie Xia, Fang Yao, Jia Huo, Junqiao Qian, Xiaomeng Liu, Langning Bai, Yu Song, Jinze Qian","doi":"10.1080/10985549.2024.2347937","DOIUrl":"10.1080/10985549.2024.2347937","url":null,"abstract":"Systemic amyloid A (AA) amyloidosis, which is considered the second most common form of systemic amyloidosis usually takes place several years prior to the occurrence of chronic inflammation, generally involving the kidney. Activated HSF1, which alleviated unfolded protein response (UPR) or enhanced HSR, is the potential therapeutic target of many diseases. However, the effect of HSF1 on AA amyloidosis remains unclear. This study focused on evaluating effect of HSF1 on AA amyloidosis based on HSF1 knockout mice. As a result, aggravated amyloid deposits and renal dysfunction have been found in HSF1 knockout mice. In progressive AA amyloidosis, HSF1 deficiency enhances serum amyloid A production might to lead to severe AA amyloid deposition in mice, which may be related to deactivated unfolded protein response as well as enhanced inflammation. Thus, HSF1 plays a significant role on UPR related pathway impacting AA amyloid deposition, which can mitigate amyloidogenic proteins from aggregation pathologically and is the possible way for intervening with the pathology of systemic amyloid disorder. In conclusion, HSF1 could not only serve as a new target for AA amyloidosis treatment in the future, but HSF1 knockout mice also can be considered as a valuable novel animal model for renal AA amyloidosis.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"165-177"},"PeriodicalIF":3.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11123510/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140958492","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}

引用次数: 0

TCF12 Transcriptionally Activates SPHK1 to Induce Osteosarcoma Angiogenesis by Promoting the S1P/S1PR4/STAT3 Axis. TCF12 通过促进 S1P/S1PR4/STAT3 轴转录激活 SPHK1 以诱导骨肉瘤血管生成

IF 3.2 2区生物学

Molecular and Cellular Biology Pub Date : 2024-01-01 Epub Date: 2024-05-20 DOI: 10.1080/10985549.2024.2341781

Wo Li, Jitong Liu, Ting Cai, Xia Hu

{"title":"TCF12 Transcriptionally Activates SPHK1 to Induce Osteosarcoma Angiogenesis by Promoting the S1P/S1PR4/STAT3 Axis.","authors":"Wo Li, Jitong Liu, Ting Cai, Xia Hu","doi":"10.1080/10985549.2024.2341781","DOIUrl":"10.1080/10985549.2024.2341781","url":null,"abstract":"Transcription factor 12 (TCF12) is a known oncogene in many cancers. However, whether TCF12 can regulate malignant phenotypes and angiogenesis in osteosarcoma is not elucidated. In this study, we demonstrated increased expression of TCF12 in osteosarcoma tissues and cell lines. High TCF12 expression was associated with metastasis and poor survival rate of osteosarcoma patients. Knockdown of TCF12 reduced the proliferation, migration, and invasion of osteosarcoma cells. TCF12 was found to bind to the promoter region of sphingosine kinase 1 (SPHK1) to induce transcriptional activation of SPHK1 expression and enhance the secretion of sphingosine-1-phosphate (S1P), which eventually resulted in the malignant phenotypes of osteosarcoma cells. In addition, S1P secreted by osteosarcoma cells promoted the angiogenesis of HUVECs by targeting S1PR4 on the cell membrane to activate the STAT3 signaling pathway. These findings suggest that TCF12 may induce transcriptional activation of SPHK1 to promote the synthesis and secretion of S1P. This process likely enhances the malignant phenotypes of osteosarcoma cells and induces angiogenesis via the S1PR4/STAT3 signaling pathway.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"178-193"},"PeriodicalIF":3.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11123469/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141065035","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}

引用次数: 0