Molecular and Cellular Biology最新文献

Understanding the Impact of Mutations in the Cystathionine Beta-Synthase Gene: Towards Novel Therapeutics for Homocystinuria. 了解胱氨酸-合成酶基因突变的影响：探索同型半胱氨酸尿的新疗法。

IF 3.2 2区生物学

Molecular and Cellular Biology Pub Date : 2025-06-10 DOI: 10.1080/10985549.2025.2511338

Tomas Majtan, Ela Mijatovic, Maria Petrosino

{"title":"Understanding the Impact of Mutations in the Cystathionine Beta-Synthase Gene: Towards Novel Therapeutics for Homocystinuria.","authors":"Tomas Majtan, Ela Mijatovic, Maria Petrosino","doi":"10.1080/10985549.2025.2511338","DOIUrl":"https://doi.org/10.1080/10985549.2025.2511338","url":null,"abstract":"Protein misfolding and conformational instability drive protein conformational disorders, causing either accelerated degradation and loss-of-function, as in inherited metabolic disorders like lysosomal storage disorders, or toxic aggregation and gain-of-function, as in neurodegenerative diseases like Alzheimer's disease or amyotrophic lateral sclerosis. Classical homocystinuria (HCU), an inborn error of sulfur amino acid metabolism, results from cystathionine beta-synthase (CBS) deficiency. CBS regulates methionine conversion into metabolites critical for redox balance (cysteine, glutathione) and signaling (H2S). Pathogenic missense mutations in the CBS gene often impair folding, cofactor binding, stability or oligomerization rather than targeting the key catalytic residues of the CBS enzyme. Advances in understanding of CBS folding and assembly as well as CBS interactions with cellular proteostasis network offer potential for therapies using pharmacological chaperones (PCs), i.e., compounds facilitating proper folding, assembly or cellular trafficking. This review discusses progress in identifying PCs for HCU, including chemical chaperones, cofactors, and proteasome inhibitors. We outline future directions, focusing on high-throughput screening and structure-based drug design to develop CBS-specific PCs. These could stabilize mutant CBS, enhance its stability and restore activity, providing new treatments for HCU and possibly other conditions related to dysregulated CBS, such as cancer or Down's syndrome.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"1-16"},"PeriodicalIF":3.2,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144266709","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}

引用次数: 0

HEB Restrains Effector Gene Expression during Early CD8⁺ Memory Precursor T Cell Differentiation. HEB在早期CD8+记忆前体T细胞分化过程中抑制效应基因表达

IF 3.2 2区生物学

Molecular and Cellular Biology Pub Date : 2025-05-26 DOI: 10.1080/10985549.2025.2505730

Joanne Pui-Ting Leung, Siamak Haddadi, Michael J Geuenich, Alara Tuncer, Vivien Musiime, Chao Wang, Juan-Carlos Zúñiga-Pflücker, Kieran R Campbell, Michele K Anderson

{"title":"HEB Restrains Effector Gene Expression during Early CD8+ Memory Precursor T Cell Differentiation.","authors":"Joanne Pui-Ting Leung, Siamak Haddadi, Michael J Geuenich, Alara Tuncer, Vivien Musiime, Chao Wang, Juan-Carlos Zúñiga-Pflücker, Kieran R Campbell, Michele K Anderson","doi":"10.1080/10985549.2025.2505730","DOIUrl":"https://doi.org/10.1080/10985549.2025.2505730","url":null,"abstract":"Memory T cells are essential for maintaining long-term adaptive immunity. Memory cell precursors and short-lived effector cells emerge from undifferentiated naïve T cells directly downstream of TCR signaling but little is known about how this lineage choice is regulated at the molecular level. The transcription factor HEB is known to be an important regulator of thymic T cell development, but how it functions in peripheral T cell differentiation is poorly understood. We assessed the role of HEB in the differentiation of memory-like T cell precursors by inducing TCR signaling in CD8 T cells in the context of memory-polarizing cytokines or inflammatory conditions and found that CD8 T cells from HEB-deficient mice underwent accelerated differentiation as compared to WT cells. Transcriptomic analysis revealed aberrant upregulation of immune response genes and decreased expression of genes promoting stemness from the earliest stages of post-TCR signal activation and persisting throughout the course of differentiation. In addition, acute viral infection of HEB cKO mice resulted in enhanced memory precursor cell formation and increased effector functionality. Therefore, we have identified HEB as a central participant in the gene regulatory networks that regulate early CD8 memory T cell differentiation and effector gene expression. This study showed that naïve CD8 T cells lacking HEB exhibit increased TCR signal strength and loss of signatures of stem-ness, revealing a role for HEB in promoting immune memory.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"1-18"},"PeriodicalIF":3.2,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144142911","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}

引用次数: 0

Liver Receptor Homolog-1 Deficiency Impairs Alcohol-Associated Liver Disease Owing to Decrease of Aldehyde Dehydrogenase 1 Family Member B1 Gene Expression. 由于醛脱氢酶1家族成员B1基因表达减少，肝脏受体同源物-1缺乏损害酒精相关性肝病

IF 3.2 2区生物学

Molecular and Cellular Biology Pub Date : 2025-05-25 DOI: 10.1080/10985549.2025.2505729

Min-Hee Seo, Jae-Ho Lee, Eun-Ho Lee, Sulagna Mukherjee, Soo-Young Park, Jae-Hoon Bae, Dae-Kyu Song, Seung-Soon Im

{"title":"Liver Receptor Homolog-1 Deficiency Impairs Alcohol-Associated Liver Disease Owing to Decrease of Aldehyde Dehydrogenase 1 Family Member B1 Gene Expression.","authors":"Min-Hee Seo, Jae-Ho Lee, Eun-Ho Lee, Sulagna Mukherjee, Soo-Young Park, Jae-Hoon Bae, Dae-Kyu Song, Seung-Soon Im","doi":"10.1080/10985549.2025.2505729","DOIUrl":"https://doi.org/10.1080/10985549.2025.2505729","url":null,"abstract":"Ethanol is detoxified in the liver, and its intake causes hepatic lipid accumulation. The liver receptor homolog-1 (LRH-1) regulates lipid and bile acid metabolism, but its role in ethanol metabolism remains unclear. This study aimed to explore the relationship between ethanol-induced lipid accumulation and LRH-1. To investigate the role of LRH-1 in hepatic ethanol metabolism, LRH-1f/f and liver-specific LRH-1f/cre+ mice were fed a Lieber-DeCarli diet for 3 weeks. The results showed that ethanol-fed LRH-1f/cre+ mice exhibited increased neutral fat, total cholesterol, liver damage markers, and acetaldehyde levels. Moreover, ethanol-fed LRH-1f/cre+ mice displayed decreased fatty acid oxidation, impaired mitochondrial function, and increased reactive oxygen species levels. To identify LRH-1 targets in ethanol metabolism, RNA sequencing analysis revealed significant changes in genes involved in fatty acid metabolism between the control and ethanol groups. Notably, in the absence of LRH-1, ethanol metabolism genes showed a reduction in aldehyde dehydrogenase 1 family member b1 (ALDH1B1) expression. Furthermore, LRH-1 overexpression in HepG2 cells led to increased ALDH1B1 expression, and ChIP sequencing data confirmed the LRH-1 binding peaks in the ALDH1B1 promoter region. In conclusion, this study confirms that LRH-1 depletion results in decreased ALDH1B1 expression, leading to acetaldehyde accumulation and accelerated intrahepatic fat accumulation.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"1-14"},"PeriodicalIF":3.2,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144142913","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}

引用次数: 0

An Intrinsically Disordered Region of the FACT Subunit, Spt16, Promotes Chromatin Disassembly in Stimulating the Pre-Initiation Complex Formation at the Promoter for Transcription Initiation In Vivo. 在体内，FACT亚基Spt16的内在紊乱区域促进染色质分解，刺激转录起始启动子处的起始前复合物形成。

IF 3.2 2区生物学

Molecular and Cellular Biology Pub Date : 2025-05-23 DOI: 10.1080/10985549.2025.2501630

Priyanka Barman, Sukesh R Bhaumik

{"title":"An Intrinsically Disordered Region of the FACT Subunit, Spt16, Promotes Chromatin Disassembly in Stimulating the Pre-Initiation Complex Formation at the Promoter for Transcription Initiation In Vivo.","authors":"Priyanka Barman, Sukesh R Bhaumik","doi":"10.1080/10985549.2025.2501630","DOIUrl":"https://doi.org/10.1080/10985549.2025.2501630","url":null,"abstract":"Previous structural and biochemical studies revealed that a negatively charged intrinsically disordered region (IDR) at the C-terminal of the Spt16 subunit of an evolutionarily conserved heterodimeric histone chaperone, FACT (Facilitates chromatin transcription), interacts with histone H2A-H2B dimer, and hence interferes the interaction of DNA with histone H2A-H2B dimer. However, the functional relevance of the binding of Spt16's IDR to histone H2A-H2B dimer with impact on chromatin dynamics and transcription has not been clearly elucidated in living cells. Here, we show that Spt16's IDR facilitates the eviction of histone H2A-H2B dimer (and hence chromatin disassembly) from the inducible GAL promoters upon transcription induction. Such facilitation of chromatin disassembly by Spt16's IDR stimulates the pre-initiation complex (PIC) formation at the promoter, and hence transcription initiation. Further, we find that Spt16's IDR regulates chromatin reassembly at the coding sequence in the wake of elongating RNA polymerase II. Collectively, our results reveal that Spt16's IDR facilitates promoter chromatin disassembly for stimulation of the PIC formation for transcription initiation with additional function in chromatin reassembly at the coding sequence in the wake of elongating RNA polymerase II, thus illuminating novel IDR regulation of chromatin dynamics and transcription in vivo.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"1-20"},"PeriodicalIF":3.2,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144128156","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}

引用次数: 0

Expression of Concern: Mitogen Stimulation Cooperates with Telomere Shortening To Activate DNA Damage Responses and Senescence Signaling. 关注表达：丝裂原刺激与端粒缩短共同激活DNA损伤反应和衰老信号。

IF 3.2 2区生物学

Molecular and Cellular Biology Pub Date : 2025-02-24 DOI: 10.1080/10985549.2025.2462481

引用次数: 0

Kinase Inhibitor-Induced Cell-Type Specific Vacuole Formation in the Absence of Canonical ATG5-Dependent Autophagy Initiation Pathway. 在缺乏典型atg5依赖性自噬起始途径的情况下，激酶抑制剂诱导细胞型特异性液泡形成。

IF 3.2 2区生物学

Molecular and Cellular Biology Pub Date : 2025-01-01 Epub Date: 2025-02-02 DOI: 10.1080/10985549.2025.2454421

Susan Jose, Himanshi Sharma, Janki Insan, Khushboo Sharma, Varun Arora, Sameera Puranapanda, Sonam Dhamija, Nabil Eid, Manoj B Menon

{"title":"Kinase Inhibitor-Induced Cell-Type Specific Vacuole Formation in the Absence of Canonical ATG5-Dependent Autophagy Initiation Pathway.","authors":"Susan Jose, Himanshi Sharma, Janki Insan, Khushboo Sharma, Varun Arora, Sameera Puranapanda, Sonam Dhamija, Nabil Eid, Manoj B Menon","doi":"10.1080/10985549.2025.2454421","DOIUrl":"10.1080/10985549.2025.2454421","url":null,"abstract":"Pyridinyl-imidazole class p38 MAPKα/β (MAPK14/MAPK11) inhibitors including SB202190 have been shown to induce cell-type specific defective autophagy resulting in micron-scale vacuole formation, cell death, and tumor suppression. We had earlier shown that this is an off-target effect of SB202190. Here we provide evidence that this vacuole formation is independent of ATG5-mediated canonical autophagosome initiation. While SB202190 interferes with autophagic flux in many cell lines parallel to vacuolation, autophagy-deficient DU-145 cells and CRISPR/Cas9 gene-edited ATG5-knockout A549 cells also undergo vacuolation upon SB202190 treatment. Late-endosomal GTPase RAB7 colocalizes with these compartments and RAB7 GTP-binding is essential for SB202190-induced vacuolation. A screen for modulators of SB202190-induced vacuolation revealed molecules including multi-kinase inhibitor sorafenib as inhibitors of vacuolation and sorafenib co-treatment enhanced cytotoxicity of SB202190. Moreover, VE-821, an ATR inhibitor was found to phenocopy the cell-type specific vacuolation response of SB202190. To identify the factors determining the cell-type specificity of vacuolation induced by SB-compounds and VE-821, we compared the transcriptomics data from vacuole-forming and non-vacuole-forming cancer cell lines and identified a gene expression signature that may define sensitivity of cells to these small-molecules. Further analyses using small molecule tools and the gene signature discovered here, could reveal novel mechanisms regulating this interesting anti-cancer phenotype.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"99-115"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080547","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}

引用次数: 0

SIRT3 Deficiency Promotes Lung Endothelial Pyroptosis Through Impairing Mitophagy to Activate NLRP3 Inflammasome During Sepsis-Induced Acute Lung Injury. 在脓毒症诱导的急性肺损伤过程中，SIRT3缺陷通过损害有丝分裂来激活NLRP3炎症体，从而促进肺内皮细胞脓毒症。

IF 3.2 2区生物学

Molecular and Cellular Biology Pub Date : 2025-01-01 Epub Date: 2024-11-18 DOI: 10.1080/10985549.2024.2426282

Congmin Yan, Xin Lin, Jingting Guan, Wengang Ding, Ziyong Yue, Zhiqiang Tang, Xiangqi Meng, Bo Zhao, Zhiqiang Song, Dongmei Li, Tao Jiang

{"title":"SIRT3 Deficiency Promotes Lung Endothelial Pyroptosis Through Impairing Mitophagy to Activate NLRP3 Inflammasome During Sepsis-Induced Acute Lung Injury.","authors":"Congmin Yan, Xin Lin, Jingting Guan, Wengang Ding, Ziyong Yue, Zhiqiang Tang, Xiangqi Meng, Bo Zhao, Zhiqiang Song, Dongmei Li, Tao Jiang","doi":"10.1080/10985549.2024.2426282","DOIUrl":"10.1080/10985549.2024.2426282","url":null,"abstract":"Acute lung injury (ALI) is a major cause of death in bacterial sepsis due to endothelial inflammation and endothelial permeability defects. Mitochondrial dysfunction is recognized as a key mediator in the pathogenesis of sepsis-induced ALI. Sirtuin 3 (SIRT3) is a histone protein deacetylase involved in preservation of mitochondrial function, which has been demonstrated in our previous study. Here, we investigated the effects of SIRT3 deficiency on impaired mitophagy to promote lung endothelial cells (ECs) pyroptosis during sepsis-induced ALI. We found that 3-TYP aggravated sepsis-induced ALI with increased lung ECs pyroptosis and enhanced NLRP3 activation. Mitochondrial reactive oxygen species (mtROS) and extracellular mitochondrial DNA (mtDNA) released from damaged mitochondria could be exacerbated in SIRT3 deficiency, which further elicit NLRP3 inflammasome activation in lung ECs during sepsis-induced ALI. Furthermore, Knockdown of SIRT3 contributed to impaired mitophagy via downregulating Parkin, which resulted in mitochondrial dysfunction. Moreover, pharmacological inhibition NLRP3 or restoration of SIRT3 attenuates sepsis-induced ALI and sepsis severity in vivo. Taken together, our results demonstrated SIRT3 deficiency facilitated mtROS production and cytosolic release of mtDNA by impaired Parkin-dependent mitophagy, promoting to lung ECs pyroptosis through the NLRP3 inflammasome activation, which providing potential therapeutic targets for sepsis-induced ALI.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"1-16"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142647859","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}

引用次数: 0

Key Mechanisms in Lysosome Stability, Degradation and Repair. 溶酶体稳定性、降解和修复的关键机制。

IF 3.2 2区生物学

Molecular and Cellular Biology Pub Date : 2025-01-01 Epub Date: 2025-05-09 DOI: 10.1080/10985549.2025.2494762

Rui Zhang, Marc A Vooijs, Tom Gh Keulers

{"title":"Key Mechanisms in Lysosome Stability, Degradation and Repair.","authors":"Rui Zhang, Marc A Vooijs, Tom Gh Keulers","doi":"10.1080/10985549.2025.2494762","DOIUrl":"10.1080/10985549.2025.2494762","url":null,"abstract":"Lysosomes are organelles that play pivotal roles in macromolecule digestion, signal transduction, autophagy, and cellular homeostasis. Lysosome instability, including the inhibition of lysosomal intracellular activity and the leakage of their contents, is associated with various pathologies, including cancer, neurodegenerative diseases, inflammatory diseases and infections. These lysosomal-related pathologies highlight the significance of factors contributing to lysosomal dysfunction. The vulnerability of the lysosomal membrane and its components to internal and external stimuli make lysosomes particularly susceptible to damage. Cells are equipped with mechanisms to repair or degrade damaged lysosomes to prevent cell death. Understanding the factors influencing lysosome stabilization and damage repair is essential for developing effective therapeutic interventions for diseases. This review explores the factors affecting lysosome acidification, membrane integrity, and functional homeostasis and examines the underlying mechanisms of lysosomal damage repair. In addition, we summarize how various risk factors impact lysosomal activity and cell fate.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"212-224"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144018298","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}

引用次数: 0

Erythropoietin Production in Embryonic Neural Cells is Controlled by Hypoxia Signaling and Histone Deacetylases with an Undifferentiated Cellular State. 胚胎神经细胞中促红细胞生成素的产生受缺氧信号和未分化细胞状态组蛋白去乙酰化酶的控制。

IF 3.2 2区生物学

Molecular and Cellular Biology Pub Date : 2025-01-01 Epub Date: 2024-12-02 DOI: 10.1080/10985549.2024.2428717

Yuma Iwamura, Taku Nakai, Koichiro Kato, Hirotaka Ishioka, Masayuki Yamamoto, Ikuo Hirano, Norio Suzuki

{"title":"Erythropoietin Production in Embryonic Neural Cells is Controlled by Hypoxia Signaling and Histone Deacetylases with an Undifferentiated Cellular State.","authors":"Yuma Iwamura, Taku Nakai, Koichiro Kato, Hirotaka Ishioka, Masayuki Yamamoto, Ikuo Hirano, Norio Suzuki","doi":"10.1080/10985549.2024.2428717","DOIUrl":"10.1080/10985549.2024.2428717","url":null,"abstract":"During mammalian development, production sites of the erythroid growth factor erythropoietin (EPO) shift from the neural tissues to the liver in embryos and to the kidneys in adults. Embryonic neural EPO-producing (NEP) cells, a subpopulation of neuroepithelial and neural crest cells, express the Epo gene between embryonic day (E) 8.5 and E11.5 to promote primitive erythropoiesis in mice. While Epo gene expression in the liver and kidneys is induced under hypoxic conditions through hypoxia-inducible transcription factors (HIFs), the Epo gene regulatory mechanisms in NEP cells remain to be elucidated. Here, we confirmed the presence of cells co-expressing EPO and HIFs in mouse neural tubes, where the hypoxic microenvironment activates HIFs. Chemical activation and inhibition of HIFs demonstrated the hypoxic regulation of EPO expression in human fetal neural progenitors and mouse embryonic neural tissues. In addition, we found that histone deacetylase inhibitors can reactivate EPO production in cell lines derived from NEP cells and human neuroblastoma, as well as in mouse primary neural crest cells, while rejuvenating these cells. Furthermore, the ability of the rejuvenated cells to produce EPO was maintained in hypoxia. Thus, EPO production is controlled by epigenetic mechanisms and hypoxia signaling in the immature state of hypoxic NEP cells.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"32-45"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142770614","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}

引用次数: 0

ALYREF Promotes Progression of Intrahepatic Cholangiocarcinoma through Increasing the Level of Isocitrate Dehydrogenase 1 in an m5C-Dependent Manner. ALYREF通过以m5c依赖的方式增加异柠檬酸脱氢酶1的水平，促进肝内胆管癌的进展。

IF 3.2 2区生物学

Molecular and Cellular Biology Pub Date : 2025-01-01 Epub Date: 2025-05-14 DOI: 10.1080/10985549.2025.2490031

Zhiqiang Hao, Haixiang Yang, Wei Zhu, Dedong Yu, Yanjie Cao, Yun Wu

{"title":"ALYREF Promotes Progression of Intrahepatic Cholangiocarcinoma through Increasing the Level of Isocitrate Dehydrogenase 1 in an m5C-Dependent Manner.","authors":"Zhiqiang Hao, Haixiang Yang, Wei Zhu, Dedong Yu, Yanjie Cao, Yun Wu","doi":"10.1080/10985549.2025.2490031","DOIUrl":"https://doi.org/10.1080/10985549.2025.2490031","url":null,"abstract":"RNA 5-methylcytosine (m5C) modification has emerged as an important regulatory mechanism in the progression of human cancers, including hepatobiliary tumors. The m5C \"reader\" Aly/REF export factor (ALYREF) was recently found to be identified as a prognostic biomarker in liver cancer. However, its exact role in intrahepatic cholangiocarcinoma (ICC) progression is unclear. In this study, ALYREF was found to be upregulated in ICC tissues and cells. The gain- and loss-of-function experiments indicated that ALYREF promoted cell proliferation and invasion and suppressed cell apoptosis. Moreover, we found that isocitrate dehydrogenase 1 (IDH1), a metastatic marker of liver cancer, was also upregulated in ICC tissues, displayed a relatively strong positive correlation with the level of ALYREF, and was positively regulated by ALYREF. As an m5C \"reader\", ALYREF interacted with m5C-IDH1 mRNA and increased its stability. ALYREF knockdown partially eliminated the promotion of IDH1 on ICC cell proliferation and invasion. ALYREF positively regulated NRF2-driven glutathione synthesis in ICC cells, which was reversed by IDH1 silencing. Finally, in a xenograft tumor mouse model, knockdown of ALYREF or treatment with ivosidenib (an IDH1 inhibitor) significantly suppressed tumor growth in vivo. In conclusion, ALYREF promotes ICC progression by increasing IDH1 levels in an m5C-dependent manner.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":"45 5","pages":"198-211"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144079054","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}

引用次数: 0