Biology Direct最新文献

{"title":"GALNT9 enrichment attenuates MPP⁺-induced cytotoxicity by ameliorating protein aggregations containing α-synuclein and mitochondrial dysfunction.","authors":"Yuanwen Peng, Jun Liu, Lili Sun, Qiuying Zheng, Can Cao, Wenyong Ding, Shufeng Yang, Li Ma, Wenli Zhang","doi":"10.1186/s13062-024-00524-8","DOIUrl":"10.1186/s13062-024-00524-8","url":null,"abstract":"<p><strong>Background: </strong>GALNTs (UDP-GalNAc; polypeptide N-acetylgalactosaminyltransferases) initiate mucin-type O-GalNAc glycosylation by adding N-GalNAc to protein serine/threonine residues. Abnormalities in O-GalNAc glycosylation are involved in various disorders such as Parkinson's disease (PD), a neurodegenerative disorder. GALNT9 is potentially downregulated in PD patients.</p><p><strong>Methods: </strong>To determine whether GALNT9 enrichment ameliorates cytotoxicity related to PD-like variations, a pcDNA3.1-GALNT9 plasmid was constructed and transfected into SH-SY5Y cells to establish a GALNT9-overexpressing cell model.</p><p><strong>Results: </strong>Downregulation of GALNT9 and O-GalNAc glycosylation was confirmed in our animal and cellular models of PD-like variations. GALNT9 supplementation greatly attenuated cytotoxicity induced by MPP⁺ (1-Methyl-4-phenylpyridinium iodide) since it led to increased levels of tyrosine hydroxylase and dopamine, reduced rates of apoptosis, and significantly ameliorated MPP⁺-induced mitochondrial dysfunction by alleviating abnormal levels of mitochondrial membrane potential and reactive oxygen species. A long-lasting mPTP (mitochondrial permeability transition pores) opening and calcium efflux resulted in significantly lower activity in the cytochrome C-associated apoptotic pathway and mitophagy process, signifying that GALNT9 supplementation maintained neuronal cell health under MPP⁺ exposure. Additionally, it was found that glycans linked to proteins influenced the formation of protein aggregates containing α-synuclein, and GALNT9 supplement dramatically reduced such insoluble protein aggregations under MPP⁺ treatment. Glial GALNT9 predominantly appears under pathological conditions like PD-like variations.</p><p><strong>Conclusions: </strong>GALNT9 enrichment improved cell survival, and glial GALNT9 potentially represents a pathogenic index for PD patients. This study provides insights into the development of therapeutic strategies for the treatment of PD.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"19 1","pages":"77"},"PeriodicalIF":5.7,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11378468/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142139269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteomics and digital subtraction angiography approaches reveal CDH18 as a potential target for therapy of moyamoya disease.","authors":"Dong Guo, Yang Dong, Hongbin Li, Hongwei Li, Bo Yang","doi":"10.1186/s13062-024-00522-w","DOIUrl":"10.1186/s13062-024-00522-w","url":null,"abstract":"<p><p>Moyamoya disease, characterized by basal cerebral artery obstruction, was studied for differential protein expression to elucidate its pathogenesis. Proteomic analysis of cerebrospinal fluid from 10 patients, categorized by postoperative angiography into good and poor prognosis groups, revealed 46 differentially expressed proteins. Notably, cadherin 18 (CDH18) was the most significantly upregulated in the good prognosis group. In addition, the expression of cadherin 18 (CDH18) and phenotypic transformation-related proteins were measured by qRT-PCR and western blot. The effects of CDH18 in vascular smooth muscle cells were detected by CCK-8, EdU, transwell and wound healing assays. The overexpression of CDH18 in vascular smooth muscle cells (VSMCs) was found to inhibit proliferation, migration, and phenotypic transformation. These findings suggest CDH18 as a potential therapeutic target in moyamoya disease.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"19 1","pages":"76"},"PeriodicalIF":5.7,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11378584/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142139270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gastrin-related circRNA_0017065 promotes the proliferation and metastasis of colorectal cancer through the miR-3174/RBFOX2 axis.","authors":"Xu Wang, Tianjiao Sun, Jiapeng Fan, Xueliang Zuo, Jiading Mao","doi":"10.1186/s13062-024-00509-7","DOIUrl":"10.1186/s13062-024-00509-7","url":null,"abstract":"<p><p>Gastrin is a gastrointestinal peptide hormone that plays an important role in the progression of colorectal cancer (CRC). However, the molecular mechanism remains unclear. In this study, we identified gastrin-related circRNAs via high-throughput sequencing and selected circRNA_0017065 as the research focus. We further studied its specific role and molecular mechanism in the progression of CRC. Knockdown and overexpression of circRNA_0017065 were performed, and the biological function of circRNA_0017065 in CRC progression was studied via in vitro and in vivo functional experiments. The potential downstream target genes were subsequently identified via screening of databases and gene chip data. The expression of circRNA_0017065 in tumour tissues was significantly upregulated compared with that in adjacent normal tissues. In vitro and in vivo functional experiments revealed that the proliferation and migration of CRC cells were significantly suppressed after circRNA_0017065 knockdown, while apoptosis was promoted. After overexpression of circRNA_0017065, the proliferation and migration of CRC cells were significantly promoted, while apoptosis was inhibited. Mechanistic studies revealed that circRNA_0017065 can act as a sponge for miR-3174 and promote CRC progression via the miR-3174/RBFOX2 axis. In general, gastrin-related circRNA_0017065 plays a key role in the occurrence and development of CRC and is expected to be a potential molecular target for the treatment of CRC metastasis.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"19 1","pages":"75"},"PeriodicalIF":5.7,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11360539/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142092294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SUMO3 inhibition by butyric acid suppresses cell viability and glycolysis and promotes gemcitabine antitumor activity in pancreatic cancer.","authors":"Liming Zhu, Gang Chen, Changjing Huang, Huifeng Gao, Yilin Wang, Yehua Shen","doi":"10.1186/s13062-024-00513-x","DOIUrl":"10.1186/s13062-024-00513-x","url":null,"abstract":"<p><strong>Background: </strong>Excavation of key molecules can help identify therapeutic targets and improve the prognosis of pancreatic cancer. This study evaluated the roles of SUMO3 in cell viability, glycolysis, gemcitabine (GEM) sensitivity, and the antitumor activity of butyric acid (BA) in pancreatic cancer.</p><p><strong>Methods: </strong>The mRNA and protein levels of SUMO3 were detected by qRT-PCR, Western blot, and immunohistochemical assay. SUMO3 was silenced or overexpressed in pancreatic cancer cells with or without Wnt/β-catenin pathway inhibitor, glycolysis inhibitor, GEM, or BA treatment. Cell viability was measured using the Cell Counting Kit-8 assay. Glycolysis was measured by determining the extracellular acidification rate, ATP level, and lactate content. Apoptosis was measured by flow cytometry, and TUNEL staining was used to examine in vitro and in vivo sensitivity to GEM chemotherapy. Luciferase reporter and chromatin immunoprecipitation assays were conducted to detect the binding of the SUMO3 promoter and NF-κB p65.</p><p><strong>Results: </strong>SUMO3 was increased and associated with poor survival in pancreatic cancer. SUMO3 knockdown decreased cell viability and glycolysis in vitro and inhibited tumor growth in vivo. SUMO3 overexpression increased cell viability and glycolysis in vitro through the β-catenin pathway. SUMO3 knockdown increased GEM sensitivity, whereas SUMO3 overexpression decreased GEM sensitivity and inhibited the antitumor activity of BA. BA promoted histone acetylation and p-IκBα expression to inhibit NF-κB p65-mediated SUMO3 transcription.</p><p><strong>Conclusion: </strong>SUMO3 acted as an active molecule in cell survival and growth by enhancing glycolysis in response to either GEM or BA. The mechanism was related to the constitutive IκBα/NF-κB/SUMO3/β-catenin signaling pathway.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"19 1","pages":"74"},"PeriodicalIF":5.7,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11345958/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142055002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reprogramming hematopoietic stem cell metabolism in lung cancer: glycolysis, oxidative phosphorylation, and the role of 2-DG.","authors":"Ziqi Guo, Yaping Liu, Xin Li, Yuying Huang, Zuping Zhou, Cheng Yang","doi":"10.1186/s13062-024-00514-w","DOIUrl":"10.1186/s13062-024-00514-w","url":null,"abstract":"<p><p>Hematopoietic stem cells (HSCs) exhibit significant functional and metabolic alterations within the lung cancer microenvironment, contributing to tumor progression and immune evasion by increasing differentiation into myeloid-derived suppressor cells (MDSCs). Our aim is to analyze the metabolic transition of HSCs from glycolysis to oxidative phosphorylation (OXPHOS) in lung cancer and determine its effects on HSC functionality. Using a murine Lewis Lung Carcinoma lung cancer model, we conducted metabolic profiling of long-term and short-term HSCs, as well as multipotent progenitors, comparing their metabolic states in normal and cancer conditions. We measured glucose uptake using 2-[N-(7-Nitrobenz-2-oxa-1,3-diazol-4-yl)Amino]-2-Deoxyglucose (2-NBDG) and assessed levels of lactate, acetyl-coenzyme A, and ATP. Mitochondrial functionality was evaluated through flow cytometry, alongside the impact of the glucose metabolism inhibitor 2-DG on HSC differentiation and mitochondrial activity. HSCs under lung cancer conditions showed increased glucose uptake and lactate production, with an associated rise in OXPHOS activity, marking a metabolic shift. Treatment with 2-DG led to decreased T-HSCs and MDSCs and an increased red blood cell count, highlighting its potential to influence metabolic and differentiation pathways in HSCs. This study provides novel insights into the metabolic reprogramming of HSCs in lung cancer, emphasizing the critical shift from glycolysis to OXPHOS and its implications for the therapeutic targeting of cancer-related metabolic pathways.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"19 1","pages":"73"},"PeriodicalIF":5.7,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11344923/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142054926","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disulfidptosis-associated LncRNA signature predicts prognosis and immune response in kidney renal clear cell carcinoma.","authors":"Kangjie Xu, Dongling Li, Kangkang Ji, Yanhua Zhang, Minglei Zhang, Hai Zhou, Xuefeng Hou, Jian Jiang, Zihang Zhang, Hua Dai, Hang Sun","doi":"10.1186/s13062-024-00517-7","DOIUrl":"10.1186/s13062-024-00517-7","url":null,"abstract":"<p><strong>Background: </strong>Kidney renal clear cell carcinoma (KIRC) represents a significant proportion of renal cell carcinomas and is characterized by high aggressiveness and poor prognosis despite advancements in immunotherapy. Disulfidptosis, a novel cell death pathway, has emerged as a critical mechanism in various cellular processes, including cancer. This study leverages machine learning to identify disulfidptosis-related long noncoding RNAs (DRlncRNAs) as potential prognostic biomarkers in KIRC, offering new insights into tumor pathogenesis and treatment avenues.</p><p><strong>Results: </strong>Our analysis of data from The Cancer Genome Atlas (TCGA) led to the identification of 431 DRlncRNAs correlated with disulfidptosis-related genes. Five key DRlncRNAs (SPINT1-AS1, AL161782.1, OVCH1-AS1, AC131009.3, and AC108673.3) were used to develop a prognostic model that effectively distinguished between low- and high-risk patients with significant differences in overall survival and progression-free survival. The low-risk group had a favorable prognosis associated with a protective immune microenvironment and a better response to targeted drugs. Conversely, the high-risk group displayed aggressive tumor features and poor immunotherapy outcomes. Validation through qRT‒PCR confirmed the differential expression of these DRlncRNAs in KIRC cells compared to normal kidney cells, underscoring their potential functional significance in tumor biology.</p><p><strong>Conclusions: </strong>This study established a robust link between disulfidptosis-related lncRNAs and patient prognosis in KIRC, underscoring their potential as prognostic biomarkers and therapeutic targets. The differential expression of these lncRNAs in tumor versus normal tissue further highlights their relevance in KIRC pathogenesis. The predictive model not only enhances our understanding of KIRC biology but also provides a novel stratification tool for precision medicine approaches, improving treatment personalization and outcomes in KIRC patients.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"19 1","pages":"71"},"PeriodicalIF":5.7,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11340127/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142035291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling the unique role of TSPAN7 across tumors: a pan-cancer study incorporating retrospective clinical research and bioinformatic analysis.","authors":"Bingnan Lu, Yifan Liu, Yuntao Yao, Dawei Zhu, Xiangmin Zhang, Keqin Dong, Xiao Xu, Donghao Lv, Zihui Zhao, Haoyu Zhang, Xinyue Yang, Wenjia Fu, Runzhi Huang, Jianwei Cao, Jian Chu, Xiuwu Pan, Xingang Cui","doi":"10.1186/s13062-024-00516-8","DOIUrl":"10.1186/s13062-024-00516-8","url":null,"abstract":"<p><strong>Background: </strong>TSPAN7 is an important factor in tumor progression. However, the precise function of TSPAN7 and its role in pan-cancer are not clear.</p><p><strong>Methods: </strong>Based on Xinhua cohort incorporating 370 patients with kidney neoplasm, we conducted differential expression analysis by immunohistochemistry between tumor and normal tissues, and explored correlations of TSPAN7 with patients' survival. Subsequently, we conducted a pan-cancer study, and successively employed differential expression analysis, competing endogenous RNA (ceRNA) analysis, protein-protein interaction (PPI) analysis, correlation analysis of TSPAN7 with clinical characteristics, tumor purity, tumor genomics, tumor immunity, and drug sensitivity. Last but not least, gene set enrichment analysis was applied to identify enriched pathways of TSPAN7.</p><p><strong>Results: </strong>In Xinhua cohort, TSPAN7 expression was significantly up-regulated (P-value = 0.0019) in tumor tissues of kidney neoplasm patients. High TSPAN7 expression was associated with decreases in overall survival (OS) (P-value = 0.009) and progression-free survival (P-value = 0.009), and it was further revealed as an independent risk factor for OS (P-value = 0.0326, HR = 5.66, 95%CI = 1.155-27.8). In pan-cancer analysis, TSPAN7 expression was down-regulated in most tumors, and it was associated with patients' survival, tumor purity, tumor genomics, tumor immunity, and drug sensitivity. The ceRNA network and PPI network of TSPAN7 were also constructed. Last but not least, the top five enriched pathways of TSPAN7 in various tumors were identified.</p><p><strong>Conclusion: </strong>TSPAN7 served as a promising biomarker of various tumors, especially kidney neoplasms, and it was closely associated with tumor purity, tumor genomics, tumor immunology, and drug sensitivity in pan-cancer level.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"19 1","pages":"72"},"PeriodicalIF":5.7,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11340126/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142035292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"hsa_circ_0020093 suppresses ovarian cancer progression by modulating LRPPRC activity and miR-107/LATS2 signaling.","authors":"Yu Sun, Xiyi Chen, Yaqian Shi, Fang Teng, Chencheng Dai, Lili Ge, Juan Xu, Xuemei Jia","doi":"10.1186/s13062-024-00520-y","DOIUrl":"10.1186/s13062-024-00520-y","url":null,"abstract":"<p><p>A substantive body of evidence has demonstrated the significant roles of circular RNA (circRNA) in cancer. However, the contribution of dysregulated circRNAs to ovarian cancer (OC) remains elusive. We aim to elucidate the critical roles and mechanisms of hsa_circ_0020093, which was demonstrated to be downregulated in OC tissues in our previous study. In this study, we confirmed the decreased expression of hsa_circ_0020093 in OC tissues and cell lines and demonstrated the negative correlation between its expression and FIGO stage, abdominal implantation and CA125 level of OC patients. Through gain and loss of function studies, we confirmed the inhibitory role of hsa_circ_0020093 in ovarian tumor growth in vitro and in vivo. Mechanistically, based on the peri-nuclear accumulation of hsa_circ_0020093, we discovered the interaction between hsa_circ_0020093 and the mitochondrial protein LRPPRC by RNA pull-down, mass spectrometry, RNA Binding Protein Immunoprecipitation. As a result, qRT-PCR and transmission electron microscopy results showed that the mitochondria mRNA expression and mitochondria abundance were decreased upon hsa_circ_0020093-overexpression. Meanwhile, we also unearthed the hsa_circ_0020093/miR-107/LATS2 axis in OC according to RNA-sequencing, RIP and luciferase reporter assay data. Furthermore, LRPPRC and LATS2 are both reported as the upstream regulators of YAP, our study also studied the crosstalk between hsa_circ_0020093, LRPPRC and miR-107/LATS2, and unearthed the up-regulation of phosphorylated YAP in hsa_circ_0020093-overexpressing OC cells and xenograft tumors. Collectively, our study indicated the novel mechanism of hsa_circ_0020093 in suppressing OC progression through both hsa_circ_0020093/LRPPRC and hsa_circ_0020093/miR-107/LATS2 axes, providing a potential therapeutic target for OC patients.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"19 1","pages":"69"},"PeriodicalIF":5.7,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11337591/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142008333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel crossover and recombination hotspots massively spread across primate genomes.","authors":"Mina Ohadi, Masoud Arabfard, Safoura Khamse, Samira Alizadeh, Sara Vafadar, Hadi Bayat, Nahid Tajeddin, Ali M A Maddi, Ahmad Delbari, Hamid R Khorram Khorshid","doi":"10.1186/s13062-024-00508-8","DOIUrl":"10.1186/s13062-024-00508-8","url":null,"abstract":"<p><strong>Background: </strong>The recombination landscape and subsequent natural selection have vast consequences forevolution and speciation. However, most of the crossover and recombination hotspots are yet to be discovered. We previously reported the relevance of C and G trinucleotide two-repeat units (CG-TTUs) in crossovers and recombination.</p><p><strong>Methods: </strong>On a genome-wide scale, here we mapped all combinations of A and T trinucleotide two-repeat units (AT-TTUs) in human, consisting of AATAAT, ATAATA, ATTATT, TTATTA, TATTAT, and TAATAA. We also compared a number of the colonies formed by the AT-TTUs (distance between consecutive AT-TTUs < 500 bp) in several other primates and mouse.</p><p><strong>Results: </strong>We found that the majority of the AT-TTUs (> 96%) resided in approximately 1.4 million colonies, spread throughout the human genome. In comparison to the CG-TTU colonies, the AT-TTU colonies were significantly more abundant and larger in size. Pure units and overlapping units of the pure units were readily detectable in the same colonies, signifying that the units were the sites of unequal crossover. We discovered dynamic sharedness of several of the colonies across the primate species studied, which mainly reached maximum complexity and size in human.</p><p><strong>Conclusions: </strong>We report novel crossover and recombination hotspots of the finest molecular resolution, massively spread and shared across the genomes of human and several other primates. With respect to crossovers and recombination, these genomes are far more dynamic than previously envisioned.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"19 1","pages":"70"},"PeriodicalIF":5.7,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11340189/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142016341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"METTL3 in cancer-associated fibroblasts-derived exosomes promotes the proliferation and metastasis and suppresses ferroptosis in colorectal cancer by eliciting ACSL3 m6A modification.","authors":"Hongtao Ren, Mincong Wang, Xiulong Ma, Lei An, Yuyan Guo, Hongbing Ma","doi":"10.1186/s13062-024-00511-z","DOIUrl":"10.1186/s13062-024-00511-z","url":null,"abstract":"<p><strong>Background: </strong>Cancer-associated fibroblasts (CAFs) have been reported that can affect cancer cell proliferation, metastasis, ferroptosis, and immune escape. METTL3-mediated N6-methyladenine (m6A) modification is involved in the tumorigenesis of colorectal cancer (CRC). Herein, we investigated whether METTL3-dependent m6A in CAFs-derived exosomes (exo) affected CRC progression.</p><p><strong>Methods: </strong>qRT-PCR and western blotting analyses detected levels of mRNAs and proteins. Cell proliferation and metastasis were evaluated using MTT, colony formation, transwell, and wound healing assays, respectively. Cell ferroptosis was assessed by detecting cell viability and the levels of Fe+, reactive oxygen species, and glutathione after erastin treatment. Exosomes were isolated from CAFs by ultracentrifugation. The m6A modification profile was determined by methylated RNA immunoprecipitation assay and the interaction between METTL3 and ACSL3 (acyl-CoA synthetase 3) was verified using dual-luciferase reporter assay. Animal models were established for in vivo analysis.</p><p><strong>Results: </strong>CAFs promoted CRC cell proliferation and metastasis, and suppressed cell ferroptosis. METTL3 was enriched in CAFs and was packaged into exosomes. The m6A modification and METTL3 expression were increased in CRC samples. Knockdown of METTL3 in CAFs-exo suppressed CRC cell proliferation and metastasis, and induced cell ferroptosis. Mechanistically, METTL3 induced ACSL3 m6A modification and stabilized its expression. The anticancer effects mediated by METTL3-silenced CAFs-exo could be rescued by ACSL3 overexpression. Moreover, in vivo assay also showed that CAFs-exo with decreased METTL3 could hinder CRC growth and metastasis in mice models.</p><p><strong>Conclusion: </strong>CAFs promoted the proliferation and metastasis, and restrained the ferroptosis in CRC by exosomal METTL3-elicited ACSL3 m6A modification.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"19 1","pages":"68"},"PeriodicalIF":5.7,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11331890/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142003627","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}