Genes & Diseases最新文献

{"title":"Gene interactions analysis of brain spatial transcriptome for Alzheimer's disease","authors":"","doi":"10.1016/j.gendis.2024.101337","DOIUrl":"10.1016/j.gendis.2024.101337","url":null,"abstract":"<div><p>Recent studies have explored the spatial transcriptomics patterns of Alzheimer's disease (AD) brain by spatial sequencing in mouse models, enabling the identification of unique genome-wide transcriptomic features associated with different spatial regions and pathological status. However, the dynamics of gene interactions that occur during amyloid-β accumulation remain largely unknown. In this study, we performed analyses on ligand-receptor communication, transcription factor regulatory network, and spot-specific network to reveal the dependence and the dynamics of gene associations/interactions on spatial regions and pathological status with mouse and human brains. We first used a spatial transcriptomics dataset of the <em>App</em>^{<em>NL-G-F</em>} knock-in AD and wild-type mouse model. We revealed 17 ligand-receptor pairs with opposite tendencies throughout the amyloid-β accumulation process and showed the specific ligand-receptor interactions across the hippocampus layers at different extents of pathological changes. We then identified nerve function related transcription factors in the hippocampus and entorhinal cortex, as well as genes with different transcriptomic association degrees in AD versus wild-type mice. Finally, another independent spatial transcriptomics dataset from different AD mouse models and human single-nuclei RNA-seq data/AlzData database were used for validation. This is the first study to identify various gene associations throughout amyloid-β accumulation based on spatial transcriptomics, establishing the foundations to reveal advanced and in-depth AD etiology from a novel perspective based on the comprehensive analyses of gene interactions that are spatio-temporal dependent.</p></div>","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":"11 6","pages":"Article 101337"},"PeriodicalIF":6.9,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S235230422400134X/pdfft?md5=1fbf3a2d47134eb845118f0f1e520f08&pid=1-s2.0-S235230422400134X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141131079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IRF8 aggravates nonalcoholic fatty liver disease via BMAL1/PPARγ axis","authors":"Xinyue Li ,&nbsp;Hong Zhang ,&nbsp;Fan Yu ,&nbsp;Shuting Xie ,&nbsp;Tongyu Wang ,&nbsp;Rong Zhang ,&nbsp;Guangzhong Xu ,&nbsp;Liang Wang ,&nbsp;Yeping Huang ,&nbsp;Cheng Hu","doi":"10.1016/j.gendis.2024.101333","DOIUrl":"10.1016/j.gendis.2024.101333","url":null,"abstract":"<div><div>Non-alcoholic fatty liver disease (NAFLD) is a hepatic metabolic syndrome arising from lipid metabolic imbalance, with its prevalence increasing globally. In this study, we observed a significant up-regulation of interferon regulatory factor 8 (IRF8) in the liver of NAFLD model mice and patients. Overexpression of IRF8 induced lipid accumulation in the mouse primary hepatocytes. Mice with adeno-associated virus-mediated IRF8 overexpression exhibited hepatic steatosis due to up-regulated peroxisome proliferator-activated receptor γ (PPARγ) expression and increased fatty acid uptake and lipogenesis. <em>In vitro</em>, small interfering RNA-mediated IRF8 knockdown attenuated triglyceride accumulation by dampening PPARγ expression through transcriptional inhibition of brain and muscle ARNT-like 1. The PPARγ-specific antagonist GW9662 abolished the effect of IRF8 overexpression. Furthermore, adeno-associated virus-mediated IRF8 knockdown in the mouse liver markedly alleviated hepatic steatosis and obesity-related metabolic syndrome. These findings indicate that IRF8 plays a vital role in modulating hepatic lipid metabolism in a PPARγ-dependent manner and provide a previously unknown insight into NAFLD therapeutic strategies.</div></div>","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":"12 3","pages":"Article 101333"},"PeriodicalIF":6.9,"publicationDate":"2024-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141138580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cancer-associated fibroblasts derived fibronectin extra domain A promotes sorafenib resistance in hepatocellular carcinoma cells by activating SHMT1","authors":"","doi":"10.1016/j.gendis.2024.101330","DOIUrl":"10.1016/j.gendis.2024.101330","url":null,"abstract":"<div><p>Resistance to sorafenib, an effective first-line treatment for advanced hepatocellular carcinoma (HCC), greatly compromised the prognosis of patients. The extracellular matrix is one of the most abundant components of the tumor microenvironment. Beyond acting as a physical barrier, it remains unclear whether cell interactions and signal transduction mediated by the extracellular matrix contribute to sorafenib resistance. With the analysis of primary HCC organoid RNA-seq data combined with <em>in vivo</em> and <em>in vitro</em> experiments validation, we discovered that fibronectin extra domain A (FN-EDA) derived from cancer-associated fibroblasts played a critical role in sorafenib resistance. Mechanistically, FN-EDA stimulates the up-regulation of the key one-carbon metabolism enzyme SHMT1 in HCC cells via the TLR4/NF-κB signaling pathway, thereby countering the oxidative stress induced by sorafenib. Moreover, we reinforced the clinical significance of our discoveries by conducting <em>in vivo</em> assays with an immunodeficiency subcutaneous xenograft tumor model, which was established using primary cancer-associated fibroblasts derived from clinical HCC tissues, and through the analysis of HCC samples obtained from The Cancer Genome Atlas (TCGA) database. Our findings suggest that targeting the FN-EDA/SHMT1 pathway could be a potential strategy to improve sorafenib responsiveness in HCC patients.</p></div>","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":"11 6","pages":"Article 101330"},"PeriodicalIF":6.9,"publicationDate":"2024-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352304224001272/pdfft?md5=6730558c8014bf0d03ae3760faddee2e&pid=1-s2.0-S2352304224001272-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141131633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardiomyocyte proliferation: Advances and insights in macrophage-targeted therapy for myocardial injury","authors":"Tao Wang ,&nbsp;Xueyao Wang ,&nbsp;Weibin Ren ,&nbsp;Zeyu Sun ,&nbsp;Yanhui Zhang ,&nbsp;Nanping Wu ,&nbsp;Hongyan Diao","doi":"10.1016/j.gendis.2024.101332","DOIUrl":"10.1016/j.gendis.2024.101332","url":null,"abstract":"<div><div>In the mammalian heart, cardiomyocytes undergo a transient window of proliferation that leads to regenerative impairment, limiting cardiomyocyte proliferation and myocardial repair capacity. Cardiac developmental patterns exacerbate the progression of heart disease characterized by myocardial cell loss, ultimately leading to cardiac dysfunction and heart failure. Myocardial infarction causes the death of partial cardiomyocytes, which triggers an immune response to remove debris and restore tissue integrity. Interestingly, when transient myocardial injury triggers irreversible loss of cardiomyocytes, the subsequent macrophages responsible for proliferation and regeneration have a unique immune phenotype that promotes the formation of pre-existing new cardiomyocytes. During mammalian regeneration, mononuclear-derived macrophages and self-renewing resident cardiac macrophages provide multiple cytokines and molecular signals that create a regenerative environment and cellular plasticity capacity in postnatal cardiomyocytes, a pivotal strategy for achieving myocardial repair. Consistent with other human tissues, cardiac macrophages originating from the embryonic endothelium produce a hierarchy of contributions to monocyte recruitment and fate specification. In this review, we discuss the novel functions of macrophages in triggering cardiac regeneration and repair after myocardial infarction and provide recent advances and prospective insights into the phenotypic transformation and heterogeneous features involving cardiac macrophages. In conclusion, macrophages contribute critically to regeneration, repair, and remodeling, and are challenging targets for cardiovascular therapeutic interventions.</div></div>","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":"12 3","pages":"Article 101332"},"PeriodicalIF":6.9,"publicationDate":"2024-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141137072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigation of the genome-wide signatures underlying the micropapillary carcinoma components in colorectal cancers","authors":"Yingying Meng ,&nbsp;Zhao Zhang ,&nbsp;Tao Tang ,&nbsp;Yanhong Yu ,&nbsp;Dan Wang ,&nbsp;Wei Sun","doi":"10.1016/j.gendis.2024.101331","DOIUrl":"10.1016/j.gendis.2024.101331","url":null,"abstract":"","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":"12 2","pages":"Article 101331"},"PeriodicalIF":6.9,"publicationDate":"2024-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141138946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of hypermethylated CpG sites mapped to LIFR as specific diagnostic biomarkers of colon cancer","authors":"Ruizhi Chang ,&nbsp;Ganxun Li ,&nbsp;Guan-nan Jin ,&nbsp;Bixiang Zhang,&nbsp;Ze-yang Ding","doi":"10.1016/j.gendis.2024.101334","DOIUrl":"10.1016/j.gendis.2024.101334","url":null,"abstract":"","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":"12 2","pages":"Article 101334"},"PeriodicalIF":6.9,"publicationDate":"2024-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141143636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of ITGA2 suppresses cervical tumorigenesis and metastasis by targeting the AKT/mTOR signaling pathway","authors":"Haixia Luo ,&nbsp;Jingjing Chang ,&nbsp;Yiting Ren ,&nbsp;Xiu Zhang ,&nbsp;Yuanxing Li ,&nbsp;Miao Huo ,&nbsp;Hongyuan Wang ,&nbsp;Xin Yang ,&nbsp;Jianbing Liu ,&nbsp;Qingmei Zhang ,&nbsp;Yueyang Zhao ,&nbsp;Wei Wang","doi":"10.1016/j.gendis.2024.101328","DOIUrl":"10.1016/j.gendis.2024.101328","url":null,"abstract":"","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":"12 2","pages":"Article 101328"},"PeriodicalIF":6.9,"publicationDate":"2024-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141135213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SNORD3B-2 promotes endometrial carcinoma progression by 2′-O-methylation modification of PLK1 and regulating RAB17 alternative splice","authors":"Xi Chen ,&nbsp;Yuping Du ,&nbsp;Bumin Xie ,&nbsp;Qianhui Li ,&nbsp;Yumeng Ji ,&nbsp;Yang Han ,&nbsp;Xiujie Sheng ,&nbsp;Shuo Chen ,&nbsp;Yang Zhao","doi":"10.1016/j.gendis.2024.101329","DOIUrl":"10.1016/j.gendis.2024.101329","url":null,"abstract":"","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":"12 2","pages":"Article 101329"},"PeriodicalIF":6.9,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141052145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"tRNA-derived small RNAs in digestive tract diseases: Progress and perspectives","authors":"Mingrui Liu ,&nbsp;Xiaojun Zhuang ,&nbsp;Haiqing Zhang ,&nbsp;Weidong Ji ,&nbsp;Gang Yuan","doi":"10.1016/j.gendis.2024.101326","DOIUrl":"10.1016/j.gendis.2024.101326","url":null,"abstract":"<div><div>tRNA-derived small RNAs (tsRNAs) are non-coding small RNAs that are produced through the precise cleavage of tRNA molecules under specific conditions. tsRNA has multiple functions, including inhibiting translation, acting in association with classical small RNA effector mechanisms, or acting in conjunction with Argonaute proteins that affect cell proliferation, migration, cycle, and apoptosis. Recent studies have revealed the clinical potential of tsRNAs in numerous diseases. This article aims to provide a comprehensive and up-to-date review of the classification and biological function of tsRNAs in gastrointestinal diseases. Furthermore, this review explores the underlying mechanisms by which tsRNAs are believed to exert their effects in both tumor and non-tumor digestive tract diseases. Therefore, specific tsRNAs prove promising for disease diagnosis, prognosis prediction, and therapeutic interventions as novel biomarkers for digestive tract diseases.</div></div>","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":"12 3","pages":"Article 101326"},"PeriodicalIF":6.9,"publicationDate":"2024-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141046069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The scRNA-sequencing landscape of pancreatic ductal adenocarcinoma revealed distinct cell populations associated with tumor initiation and progression","authors":"Ying Wang ,&nbsp;Zhouliang Bian ,&nbsp;Lichao Xu ,&nbsp;Guangye Du ,&nbsp;Zihao Qi ,&nbsp;Yanjie Zhang ,&nbsp;Jiang Long ,&nbsp;Wentao Li","doi":"10.1016/j.gendis.2024.101323","DOIUrl":"10.1016/j.gendis.2024.101323","url":null,"abstract":"<div><div>Pancreatic ductal adenocarcinoma (PDAC) stands as a formidable malignancy characterized by its profound lethality. The comprehensive analysis of the transcriptional landscape holds immense significance in understanding PDAC development and exploring novel treatment strategies. However, due to the firm consistency of pancreatic cancer samples, the dissociation of single cells and subsequent sequencing can be challenging. Here, we performed single-cell RNA sequencing (scRNA-seq) on 8 PDAC patients with different lymph node metastasis status. We first identified the crucial role of <em>MMP1</em> in the transition from normal pancreatic cells to cancer cells. The knockdown of <em>MMP1</em> in pancreatic cancer cell lines decreased the expression of ductal markers such as <em>SOX9</em> while the overexpression of <em>MMP1</em> in hTERT-HPNE increased the expression of ductal markers, suggesting its function of maintaining ductal identity. Secondly, we found a <em>S100A2</em>⁺ tumor subset which fueled lymph node metastasis in PDAC. The knockdown of <em>S100A2</em> significantly reduced the motility of pancreatic cancer cell lines in both wound healing and transwell migration assays. While overexpression of <em>S100A2</em> led to increased migratory capability. Moreover, overexpression of <em>S100A2</em> in KPC1199, a mouse pancreatic cancer cell line, caused a larger tumor burden in a hemi-spleen injection model of liver metastasis. In addition, epithelial-mesenchymal transition-related genes were decreased by <em>S100A2</em> knockdown revealed by bulk RNA sequencing. We also identified several pivotal contributors to the pro-tumor microenvironment, notably <em>OMD</em>⁺ fibroblast and <em>CCL2</em>⁺ macrophage. As a result, our study provides valuable insights for early detection of PDAC and promising therapeutic targets for combatting lymph node metastasis.</div></div>","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":"12 3","pages":"Article 101323"},"PeriodicalIF":6.9,"publicationDate":"2024-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141044854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}