Journal of Advanced Research最新文献

{"title":"Functions of FGF21 and its role in cardiac hypertrophy","authors":"Lei Chen, Meng Gao, Sang-Bing Ong, Guohua Gong","doi":"10.1016/j.jare.2025.03.007","DOIUrl":"https://doi.org/10.1016/j.jare.2025.03.007","url":null,"abstract":"<h3>Background</h3>FGF21 is a stress-inducible hormone that operates in the autocrine or paracrine manner. Recent reports have revealed that FGF21 is highly expressed in cardiac hypertrophy to protect against heart injury and dysfunction. FGF21 is used to treat cardiac hypertrophy in mouse models. However, preclinical and clinical trials are restricted.<h3>Aim of review</h3>This review mainly elucidates the diverse functions of FGF21 and explores the relationship between these functions and cardiac hypertrophy. It also discusses challenges and future perspectives in treating cardiac hypertrophy with FGF21.<h3>Key Scientific Concepts of Review</h3>This review first illustrates the functions of FGF21, including energy metabolism, inflammation, oxidative stress, apoptosis, and autophagy. We also summarize vital functions and the underlying mechanisms through which FGF21 regulates the initiation and development of cardiac hypertrophy, connecting energy metabolism, inflammation, oxidative stress, apoptosis, and autophagy. Finally, we propose that FGF21 may be a potential therapeutic strategy for cardiac hypertrophy.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"10 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143618832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alarm: Retracted articles on cancer imaging are not only continuously cited by publications but also used by ChatGPT to answer questions","authors":"Tianshu Gu, Helin Feng, Minghui Li, Weikuan Gu, Guiying Wang","doi":"10.1016/j.jare.2025.03.020","DOIUrl":"https://doi.org/10.1016/j.jare.2025.03.020","url":null,"abstract":"One of the most widely used applications of AI in cancer treatment is in the assistance of imaging [<span><span>[1]</span></span>, <span><span>[2]</span></span>]. Imaging is vital for identifying conditions of different kinds of cancer and improving treatment outcomes [<span><span>[3]</span></span>, <span><span>[4]</span></span>, <span><span>[5]</span></span>]. AI algorithms enhance the interpretation of medical images, leading to more accurate and timely diagnoses of cancer. Machine learning models assist in detecting anomalies in radiology, pathology, and dermatology images, thereby improving diagnostic precision of cancer and patient outcomes. Researchers have contributed to the development of AI methods for medical imaging, including MRI techniques for determining flow and motion [<span><span>2</span></span>].","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"56 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143599249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Trained immunity using probiotics and inactivated pathogens enhances resistance to Salmonella enterica serovar Typhimurium infection by activating the cGAS-STING signal pathway in mice and chickens","authors":"Junpeng Jia, Wenxin Ji, Ningna Xiong, Jian Lin, Qian Yang","doi":"10.1016/j.jare.2025.03.011","DOIUrl":"https://doi.org/10.1016/j.jare.2025.03.011","url":null,"abstract":"<h3>Introduction</h3>Concerns about antibiotic resistance have prompted interest in alternative strategies for enhancing disease resistance, particularly in livestock and poultry production.<h3>Objectives</h3>This study explored the role of trained immunity in enhancing resistance to S<em>almonella enterica</em> serovar Typhimurium (S. Typhimurium) infection in mice and chickens.<h3>Methods</h3>We investigated the effects of probiotics and inactivated pathogenic bacterial strains on host immunity in <em>Toll-like receptor 2</em>-deficient mice (TLR2⁻/⁻) to assess whether these effects were related to bacterial outer membrane components such as peptidoglycan (<em>PNG</em>), lipoarabinomannan (<em>LAM</em>) and lipoteichoic acid (<em>LTA</em>). Bacterial genomes were evaluated for their ability to enhance the host immune system. Macrophage-depletion models were used to identify the key immune cells involved in trained immunity, with a focus on the cGAS-STING pathway.<h3>Results</h3>Probiotics and inactivated pathogenic strains enhanced host immunity and protected against S. Typhimurium infection. As demonstrated in the <em>TLR2</em>-deficient mice, the effects were not dependent on bacterial outer membrane components. Instead, bacterial genomes played a significant role in activating trained immunity. Macrophages were identified as the primary cells that mediated the response with the cGAS-STING pathway playing a crucial role. The results observed using the mouse models led to investigating the potential application of trained immunity in poultry.<h3>Conclusion</h3>Trained immunity activated by probiotics and inactivated bacterial pathogens enhanced resistance against S. Typhimurium infection via macrophage activation and involved the cGAS-STING pathway. These findings highlight the potential of trained immunity as an alternative strategy for disease prevention in both livestock and poultry.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"17 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143599195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SAMD4A inhibits abdominal aortic aneurysm development and VSMC phenotypic transformation through targeting KDM2B","authors":"Qing Chen, Shenrong Liu, Haobin Zhou, Junfen Wang, Xiaoyong Xiao, Guojun Chen, Juan Du, Lintao Zhong, Haoyu Song, Xianying Huang","doi":"10.1016/j.jare.2025.03.018","DOIUrl":"https://doi.org/10.1016/j.jare.2025.03.018","url":null,"abstract":"<h3>Introduction</h3>Abdominal aortic aneurysm (AAA) is a fatal vascular disease without effective drug treatments. Pathological vascular smooth muscle cell (VSMC) phenotypic transformation is the underlying cause of AAA. However, the underlying mechanism has not been fully elucidated.<h3>Objective</h3>We aimed to determine whether the RNA binding protein SAMD4A suppresses VSMC phenotype transformation and inhibits AAA formation.<h3>Methods</h3>Single-cell RNA sequencing (scRNA-seq) was conducted to reveal smooth muscle cell phenotypic heterogeneity and RNA-binding protein dysregulation during AAA formation. A pancreatic elastase (PPE)-induced mouse AAA model was generated to confirm the function of SAMD4A in vivo. RNA-seq combined with RNA immunoprecipitation (RIP) sequencing and chromatin immunoprecipitation (ChIP)–qPCR was used for mechanistic exploration.<h3>Results</h3>We identified 3 smooth muscle cell subtypes, and demonstrated their transformation from contractile to inflammatory-like VSMCs during AAA formation. SAMD4A expression was increased in contractile VSMCs and significantly reduced in AAAs. The results of functional experiments revealed that VSMC-specific knockout of SAMD4A exacerbated PPE-induced AAA formation, whereas VSMC knock-in attenuated AAA formation. SAMD4A regulated VSMC contraction by binding to KDM2B. Further in vivo studies revealed that overexpression of KDM2B abolished the protective effect of SAMD4A in AAA. ChIP–qPCR demonstrated that KDM2B suppressed the transcription of VSMC contractile markers by binding to their promoters and reducing H3K4me3 and H3K36me2 levels.<h3>Conclusions</h3>SAMD4A inhibits AAA development and VSMC phenotypic transformation by targeting KDM2B. This work highlights the potential of SAMD4A as a new therapeutic option to prevent AAA formation.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"56 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143590217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Meta-analyses of the global impact of non-antibiotic feed additives on livestock performance and health","authors":"Lily Liu, Pengfei Wang, Songlin Liu, Min Yan, Qin Zhang, Emily Clark, Jinhai Wang","doi":"10.1016/j.jare.2025.03.009","DOIUrl":"https://doi.org/10.1016/j.jare.2025.03.009","url":null,"abstract":"<h3>Introduction</h3>The impact of non-antibiotic feed additives on livestock performance and health is contingent upon a multitude of variables, including the animal species, dosage and type of feed additives, and duration of oral administration. However, there is a paucity of knowledge regarding the relationship between these factors and the performance of livestock animals.<h3>Objectives</h3>The objective of this study was to conduct a global <em>meta</em>-analysis based on a pool of empirical studies to investigate the effects of dietary additives on growth, production, blood metabolites, immunity, intestinal morphology, and the abundance of gut microbiota in livestock.<h3>Methods</h3>A <em>meta</em>-regression coupled with dose–effect analysis was performed to ascertain the optimal dosage and feeding duration for the optimal body function. A total of 71 papers, estimating 1, 035 effect size across 9 species and 7 types of non-antibiotic feed additives were recruited in our <em>meta</em>-dataset.<h3>Results</h3>Overall assessment confirmed that these additives in diet can significantly improve livestock production and immune function across species. Our findings indicated that the effects of additives on animal performance were more pronounced in herbivores than in omnivores. The dose–response results indicated that the overall optimal doses for antimicrobial peptides, enzymes, oligosaccharides, organic acids, phytogenic, probiotics and prebiotics were 100 mg/kg, 30 mg/kg, 200 mg/kg, 50 mg/kg, 200 mg/kg, 10⁶ CFU/kg, and 10 mg/kg, respectively. Oral administration of these additives for a 2-month period effectively improves livestock performance and health.<h3>Conclusion</h3>This evidence-based approach provides a foundation for implementing customized feeding strategies designed to optimize livestock performance, enhance immunity and reduce feed costs. Our assessment shows that these feed additives are promising alternatives to antibiotics in reducing the use of antibiotics. Furthermore, these findings suggest that the use of these feed additives can lead to evidence-based recommendations for practical feeding strategies, providing livestock producers with a sustainable and cost-effective approach to animal health management.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"40 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143590219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discovery and identification of semaphorin 4D as a bioindicator of high fracture incidence in type 2 diabetic mice with glucose control","authors":"Xuanchen Liu, Mo Wang, Bin Xu, Xue Ma, Yangzi Jiang, Hai Huang, Zengzeng Shi, Hao Wu, Zhigang Wu, Shuo Guo, Jungang Zhao, Jian Zhao, Xiaokang Li, Li Liang, Zheng Guo, Lei Shi, Chao Sun, Ning Wang","doi":"10.1016/j.jare.2025.03.014","DOIUrl":"https://doi.org/10.1016/j.jare.2025.03.014","url":null,"abstract":"<h3>Introduction</h3>Bone fracture is increasing in patients with type 2 diabetes mellitus (T2DM) due to skeletal fragility. Most antidiabetics are expected to reduce the incidence of fracture in patients with T2DM, however the results are disappointing. Metformin and GLP-1 receptor agonists have a neutral or minor positive effect in reducing fractures.<h3>Objectives</h3>We aim to reveal the mechanism of fracture in patients with T2DM treated with metformin or exendin-4, explore the key regulators responsible for bone fragility in T2DM.<h3>Methods</h3>Trabecular and cortical masses in mice with T2DM were analyzed using micro-computed tomography. Biomechanical strength of bone was determined according to three-point bending, and the expression of bone-associated factors was examined with enzyme-linked immunosorbent assays. Important proteins and miRNAs were identified using proteomics analysis and deep screening analysis. Lastly, immunoprecipitation–mass spectrometry and dual–luciferase reporter analysis were used to identify key molecular signals.<h3>Results</h3>We found that sermaphorin 4D (Sema4D) is the key regulator of bone fragility in T2DM. Exendin-4 increased the biomechanical properties of bone by decreasing serum Sema4D levels, and metformin has little effect on Sema4D. Anti-sema4D treatment could improve bone strength in T2DM mice compared with metformin or exendin-4. The biomechanical properties of bone were comparable between anti-Sema 4D and the combination of metformin and exendin-4. Exendin-4 promoted osteogenesis of BMSCs by activating CRMP2 to reverse the effect of sema4D. Metformin increased miR-140-3p levels, which decreased plexin B1 expression in bone mesenchymal stem cells. Metformin increased the effect of exendin-4 with more GLP-1 receptor expression to increase the biomechanical strength of bone via miR-140-3p-STAT3-miR-3657 signaling.<h3>Conclusion</h3>Blood glucose level is not the major factor contributing to impairment in bone remodeling. Sema4D is responsible for the increase in the incidence of bone fractures in T2DM. Accordingly, we proposed an effective therapeutic strategy to eliminate the effect of sema4D.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"25 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143590216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neutrophil extracellular traps-triggered hepatocellular senescence exacerbates lipotoxicity in non-alcoholic steatohepatitis","authors":"Ming Xu, Hao Xu, Yu-Wei Ling, Jing-Jing Liu, Ping Song, Zhi-Qiang Fang, Zhen-Sheng Yue, Juan-Li Duan, Fei He, Lin Wang","doi":"10.1016/j.jare.2025.03.015","DOIUrl":"https://doi.org/10.1016/j.jare.2025.03.015","url":null,"abstract":"<h3>Introduction</h3>Neutrophils are initial responders in inflammation and contribute to non-alcoholic fatty liver disease (NAFLD) progression to steatohepatitis (NASH).Neutrophil extracellular traps (NETs) are implicated in liver injury, yet their precise mechanisms in NASH progression remains unclear.<h3>Objectives</h3>This study investigates how NETs drive NASH progression by disrupting hepatocyte lipotoxicity and explore the regulatory mechanism of NETs formation and its downstream effects on liver pathology.<h3>Methods</h3>Clinical samples from NASH patients and diet-induced NASH mice were analyzed for NET levels. NETs were pharmacologically inhibited, and senescent cells were selectively eliminated in mice. Myeloid-specific RBP-J knockout mice were generated to disrupt Notch signaling, with subsequent evaluation of NET formation, senescence markers, steatosis, fibrosis, and inflammation.<h3>Results</h3>NETs are elevated in NASH patients and mice, correlating with hepatocyte senescence and lipotoxicity. Pharmacological NET disruption reduced hepatocyte senescence, accompanied by attenuated steatosis and fibrosis. Senescent cell clearance replicated these improvements, confirming liver senescence emerges is a vital step for NETs to promote the progression of NASH. Myeloid-specific Notch signaling ablation suppressed NET generation, concurrently decreasing lipid deposition and liver inflammation.<h3>Conclusion</h3>Our findings elucidate a novel mechanism by which neutrophil-derived Notch driven NETs exacerbate NASH by promoting cell senescence, thereby contributing to hepatic steatosis and fibrosis. This insight may provide potential intervention strategies and therapeutic targets for NASH treatment.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"13 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143582640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"BMP9 Alleviates Iron Accumulation-Induced Osteoporosis via the USP10/FOXO1/GPX4 Axis","authors":"Yanran Huang, Jun Zhang, Yafei Zhu, Runhan Zhao, Zhou Xie, Xiao Qu, Yingtao Duan, Ningdao Li, Dagang Tang, Xiaoji Luo","doi":"10.1016/j.jare.2025.03.012","DOIUrl":"https://doi.org/10.1016/j.jare.2025.03.012","url":null,"abstract":"<h3>Introduction</h3>Ferroptosis induced by iron accumulation can disrupt the physiological functions of bone marrow mesenchymal stem cells (BMSCs). BMP9 is an effective osteogenic factor. However, the role of BMP9 and its molecular mechanisms in osteoporosis induced by iron accumulation remain unclear.<h3>Objectives</h3>This study aims to explore the role and mechanism of BMP9 in alleviating iron accumulation induced osteoporosis.<h3>Methods</h3>Clinical samples were collected to analyze the relationship between iron accumulation and osteoporosis. The effect of BMP9 on lipid peroxidation levels in BMSCs under iron accumulation conditions was assessed using C11-BODIPY staining, MitoSOX staining, MDA and SOD activity measurement. The osteogenic capacity of BMP9 in BMSCs under iron accumulation conditions was evaluated by measuring ALP activity and calcium nodule formation. The mechanisms of BMP9 in regulating BMSCs under iron accumulation conditions were explored through experiments including cycloheximide treatment, RT-PCR, Western blot, GST pull-down, ChIP, and CO-IP.<h3>Results</h3>It was observed in human samples that serum ferritin levels were negatively correlated with the bone mineral density of the lumbar spine and femoral neck. Meanwhile, ferroptosis is considered a key factor affecting bone health. Further research indicated that BMP9 could inhibit ferroptosis in cells and animal models with iron accumulation, while also improving oxidative stress and osteogenic capacity. In-depth investigation of its mechanism reveals that BMP9 promotes the expression of USP10, which removes the K48-linked ubiquitin chains on FOXO1, inhibiting its excessive ubiquitination in the cytoplasm. This stabilization allows FOXO1 to accumulate in the cytoplasm and eventually re-enter the nucleus. This process activated the expression of the key inhibitor of cell death, GPX4, enhancing the cell’s antioxidant response, reducing ferroptosis-induced damage to BMSCs, and promoting their osteogenic differentiation.<h3>Conclusion</h3>This study reveals that BMP9 inhibits ferroptosis through the USP10/FOXO1/GPX4 axis, providing a new therapeutic strategy for osteoporosis caused by iron accumulation.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"132 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143582498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reshaped local microbiology metabolism by raw tea according to pile fermentation in the dark tea","authors":"Yating Guo, Yani Pan, Xinyu Feng, Haowei Guo, Liping Liu, Kexin Zhang, Haojun Xie, Binkai Zhu, Shuying Gong, Qiang Chu, Hua Fang, Ping Chen","doi":"10.1016/j.jare.2025.02.039","DOIUrl":"https://doi.org/10.1016/j.jare.2025.02.039","url":null,"abstract":"<h3>Introduction</h3>Traditionally, the mechanism of dark tea quality formation has centered on microorganisms, with quality regulated by manipulating microorganisms and their fermentation environment. Nevertheless, raw teas, the natural selective medium of microbial community, was completely ignored in the formation of dark tea unique flavors.<h3>Objectives</h3>This study aims to uncover the previously unappreciated interactions between raw tea and microorganisms, demonstrating the significant role of raw tea in the formation of dark tea quality.<h3>Methods</h3>Sun-dried raw tea (SDT), baked raw tea (BT), and pan-fried raw tea (PFT) were pile fermented. Chemical profiles, microbial communities, and sensory qualities were assessed by metabolomics, high-throughput sequencing, and sensory evaluation, with correlation and multiple factor analyses used to explore their relationships.<h3>Results</h3>Compared to PFT and BT, SDT had 18 % lower flavonoid content and 26 % lower catechin content, which favored dominant <em>Agathobacter</em> and <em>Wickerhamomyces</em>. <em>Wickerhamomyces</em> contributed to flower aroma by producing alcohols, esters and terpenes, while <em>Agathobacter</em> amplified acid production. The distinctive dominant bacterium <em>Acidovorax</em> in BT was positively correlated with alcohols and hydrocarbons, with Pearson’s r &gt; 0.6, resulting in a 47 % increase in volatile alcohol level, enhancing the fresh and refreshing attributes. A 70–80 % increase in iron concentration in PFT compared to SDT and BT resulted in the predominance of <em>Geobacter</em>, which exhibited a negative correlation with aldehydes. The presence of distinctive bacteria, <em>Streptococcus</em> and <em>Ligilactobacillus</em>, in PFT led to a significant rise in volatile acid content, increasing from 5 % to 25 %.<h3>Conclusion</h3>The chemical profiles of raw tea could reshape local microbiota, which then drives unique qualities of dark tea. This indicates dark tea quality is not passively shaped by the environmental microorganisms, but actively screened by raw tea chemistry. This study paves the way for targeted manipulation of raw tea chemical profiles to achieve desired dark tea flavor characteristics.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"87 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143576335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SRSF9 mediates oncogenic RNA splicing of SLC37A4 via liquid–liquid phase separation to promote oral cancer progression","authors":"Qiu Peng, Lujuan Wang, Ying Long, Hao Tian, Xuemeng Xu, Zongyao Ren, Yaqian Han, Xianjie Jiang, Zhu Wu, Shiming Tan, Wenjuan Yang, Linda Oyang, Xia Luo, Jinguan Lin, Longzheng Xia, Mingjing Peng, Nayiyuan Wu, Yanyan Tang, Qianjin Liao, Yujuan Zhou","doi":"10.1016/j.jare.2025.03.013","DOIUrl":"https://doi.org/10.1016/j.jare.2025.03.013","url":null,"abstract":"<h3>Introduction</h3>Oral cancer represents a significant proportion of head and neck malignancies, accounting for approximately 3 % of all malignant tumors worldwide.<h3>Objectives</h3>Alternative splicing (AS), a post-transcriptional regulatory mechanism, is increasingly linked to cancer development. The precise impact of AS on oral cancer progression is not well understood.<h3>Methods</h3>Bioinformatics, semi-quantitative RT-PCR, and minigene reporter system to detect the skipping of SLC37A4 exon 7 in oral cancer. FRAP, live cell immunofluorescence demonstrates that SRSF9 can undergo liquid–liquid phase separation (LLPS). In vivo and in vitro experiments with subcutaneous graft tumors, CCK8, EdU, transwell, and others were used to detect the effects of SRSF9 and its induced SLC37A4-S isoforms on the malignant phenotype of oral cancer cells.<h3>Results</h3>Our investigation revealed a multitude of aberrant alternative splicing events within head and neck tumor tissues, most notably the pronounced skipping of exon 7 in the SLC37A4 gene. This splicing anomaly leads to the production of a truncated isoform, SLC37A4-S, which is associated with a poor prognosis and significantly augments the proliferation and metastatic potential of oral cancer cells relative to the wild-type isoform, SLC37A4-L. Mechanically, SRSF9 may play a regulatory role in the aberrant splicing of SLC37A4. Furthermore, SRSF9 is capable of undergoing LLPS, a process driven by its arginine-serine-rich (RS) domain. Disruption of SRSF9 LLPS through the use of inhibitors or mutants effectively prevents its regulatory influence on the splicing of SLC37A4. Significantly, our research demonstrates that both SRSF9 and its regulated splicing isoforms of SLC37A4-S contribute to cisplatin chemotherapy resistance in oral cancer cells.<h3>Conclusion</h3>This study elucidates the mechanism by which SRSF9 phase separation mediates splicing in oral cancer, thereby establishing a basis for considering SRSF9 and its associated SLC37A4-S isoforms as potential therapeutic targets for oral cancer treatment.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"3 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143576334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}