Genes & Diseases最新文献

Targeting MYC: Multidimensional regulation and therapeutic strategies in oncology 瞄准 MYC：肿瘤学中的多维调控和治疗策略

IF 6.8 2区医学

Genes & Diseases Pub Date : 2024-09-16 DOI: 10.1016/j.gendis.2024.101435

Yingying Duan, Zhaoshuo Liu, Qilin Wang, Junyou Zhang, Jiaxin Liu, Ziyi Zhang, Chunyan Li

{"title":"Targeting MYC: Multidimensional regulation and therapeutic strategies in oncology","authors":"Yingying Duan, Zhaoshuo Liu, Qilin Wang, Junyou Zhang, Jiaxin Liu, Ziyi Zhang, Chunyan Li","doi":"10.1016/j.gendis.2024.101435","DOIUrl":"https://doi.org/10.1016/j.gendis.2024.101435","url":null,"abstract":"MYC is dysregulated in approximately 70% of human cancers, strongly suggesting its essential function in cancer. MYC regulates many biological processes, such as cell cycle, metabolism, cellular senescence, apoptosis, angiogenesis, and immune escape. MYC plays a central role in carcinogenesis and is a key regulator of tumor development and drug resistance. Therefore, MYC is one of the most alluring therapeutic targets for developing cancer drugs. Although the search for direct inhibitors of MYC is challenging, MYC cannot simply be assumed to be undruggable. Targeting the MYC-MAX complex has been an effective method for directly targeting MYC. Alternatively, indirect targeting of MYC represents a more pragmatic therapeutic approach, mainly including inhibition of the transcriptional or translational processes of MYC, destabilization of the MYC protein, and blocking genes that are synthetically lethal with MYC overexpression. In this review, we delineate the multifaceted roles of MYC in cancer progression, highlighting a spectrum of therapeutic strategies and inhibitors for cancer therapy that target MYC, either directly or indirectly.","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":null,"pages":null},"PeriodicalIF":6.8,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142269436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Heavy mechanical force decelerates orthodontic tooth movement via Piezo1-induced mitochondrial calcium down-regulation 重型机械力通过 Piezo1 诱导的线粒体钙下调，使牙齿矫正运动减速

IF 6.8 2区医学

Genes & Diseases Pub Date : 2024-09-15 DOI: 10.1016/j.gendis.2024.101434

Ye Zhu, Xuehuan Meng, Qiming Zhai, Liangjing Xin, Hao Tan, Xinyi He, Xiang Li, Guoyin Yang, Jinlin Song, Leilei Zheng

{"title":"Heavy mechanical force decelerates orthodontic tooth movement via Piezo1-induced mitochondrial calcium down-regulation","authors":"Ye Zhu, Xuehuan Meng, Qiming Zhai, Liangjing Xin, Hao Tan, Xinyi He, Xiang Li, Guoyin Yang, Jinlin Song, Leilei Zheng","doi":"10.1016/j.gendis.2024.101434","DOIUrl":"https://doi.org/10.1016/j.gendis.2024.101434","url":null,"abstract":"Orthodontic tooth movement (OTM) depends on periodontal ligament cells (PDLCs), which sense biomechanical stimuli and initiate alveolar bone remodeling. Light (optimal) forces accelerate OTM, whereas heavy forces decelerate it. However, the mechanisms by which PDLCs sense biomechanical stimuli and affect osteoclastic activities under different mechanical forces (MFs) remain unclear. This study demonstrates that mechanosensitive ion channel Piezo1-mediated Ca<ce:sup loc=\"post\">2+</ce:sup> signal conversion is crucial for sensing and delivering biomechanical signals in PDLCs under heavy-force conditions. Heavy MF up-regulated Piezo1 in PDLCs, reducing mitochondrial Ca<ce:sup loc=\"post\">2+</ce:sup> influx by inhibiting ITPR3 expression in mitochondria-associated membranes. Decreased mitochondrial calcium uptake led to reduced cytoplasmic release of mitochondrial DNA and inhibited the activation of the cGAS‒STING signaling cascade, subsequently inhibiting monocyte-to-osteoclast differentiation. Inhibition of Piezo1 or up-regulation of STING expression under heavy MF conditions significantly increased osteoclast activity and accelerated OTM. These findings suggest that heavy MF-induced Piezo1 expression in PDLCs is closely related to the control of osteoclast activity during OTM and plays an essential role in alveolar bone remodeling. This mechanism may be a potential therapeutic target for accelerating OTM.","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":null,"pages":null},"PeriodicalIF":6.8,"publicationDate":"2024-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142258074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

MAFB-mediated CEBPA regulated human urothelium growth through Wnt/β-catenin signaling pathway MAFB 介导的 CEBPA 通过 Wnt/β-catenin 信号通路调控人尿路细胞的生长

IF 6.9 2区医学

Genes & Diseases Pub Date : 2024-09-13 DOI: 10.1016/j.gendis.2024.101432

{"title":"MAFB-mediated CEBPA regulated human urothelium growth through Wnt/β-catenin signaling pathway","authors":"","doi":"10.1016/j.gendis.2024.101432","DOIUrl":"10.1016/j.gendis.2024.101432","url":null,"abstract":"<div><div>MAFB is essential for regulating male-type urethral differentiation, and especially, its variation can contribute to hypospadias in mice. However, the potential mechanism is still unclear. Here we observed that the basic leucine zipper (bZIP) transcription factor MAFB and CCAAT/enhancer-binding protein alpha (CEBPA) could promote human urothelium SV-HUC-1 growth. Moreover, MAFB and CEBPA expression were reduced in the prepuce tissues of hypospadias patients. Based on transcriptome sequencing analysis and Western blot, MAFB knockdown was found to suppress CEBPA protein expression and repress Wnt/β-catenin signaling in urothelium cells. Meanwhile, we observed blocked cell-cycle progression from the G1 to the S phase, inhibited cell proliferation, and activated apoptosis. Furthermore, MAFB could facilitate CEBPA transcription and regulate the proliferation of urothelium. The above results indicated that MAFB-mediated inhibition of urothelial SV-HUC-1 growth resulted from inhibiting the Wnt/β-catenin signaling pathway by down-regulating CEBPA. Our findings provide new insight into the understanding of genes associated with hypospadias and the pathogenic mechanism of this disorder.</div></div>","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":null,"pages":null},"PeriodicalIF":6.9,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142258075","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}

引用次数: 0

HMGN2 accelerates the proliferation and cell cycle progression of glioblastoma by regulating CDC20 expression HMGN2 通过调控 CDC20 的表达加速胶质母细胞瘤的增殖和细胞周期进程

IF 6.8 2区医学

Genes & Diseases Pub Date : 2024-09-12 DOI: 10.1016/j.gendis.2024.101433

Jiacheng Zhong, Shuang Shi, Wen Peng, Hongjuan Cui, Xiaochuan Sun

{"title":"HMGN2 accelerates the proliferation and cell cycle progression of glioblastoma by regulating CDC20 expression","authors":"Jiacheng Zhong, Shuang Shi, Wen Peng, Hongjuan Cui, Xiaochuan Sun","doi":"10.1016/j.gendis.2024.101433","DOIUrl":"https://doi.org/10.1016/j.gendis.2024.101433","url":null,"abstract":"Gliomas represent the most common primary malignant intracranial tumors in adults. Despite recent advances in treatment, the prognosis of patients with glioblastoma remains poor. Epigenetic abnormalities, the hallmarks of various types of cancer, contribute to the dysregulated expression of cancer-related genes. Post-translational modification of histones plays a pivotal role in cancer development and progression by modulating gene transcription, chromatin remodeling, and nuclear structure. Therefore, further exploration of the molecular mechanisms of epigenetic regulation in gliomas and the identification of superior therapeutic targets are required. High-mobility group nucleosomal-binding domain 2 (HMGN2) participates in the epigenetic regulation of genes through histone modification and exhibits significant differential expression between glioma and normal tissues. However, the effect of HMGN2 on gliomas and its underlying mechanisms remain unclear. This study aimed to elucidate these uncertainties by demonstrating that HMGN2 significantly promotes the proliferation of glioma cells. HMGN2 binds to histones and promotes the stability of H3K27ac acetylation in the cell division cycle 20 (CDC20) promoter region, enhancing the transcriptional activity of CDC20 and increasing the proliferation of glioma cells. Moreover, we found that CDC20 expression was negatively correlated with the survival time of patients with glioma. These results suggest that targeting epigenetic regulation, such as the HMGN2/CDC20 axis, may provide a novel direction for the treatment of gliomas.","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":null,"pages":null},"PeriodicalIF":6.8,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142258076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Systematic pan-cancer analysis identifies DNASE2 as a potential prognostic marker and immunotherapeutic target for glioblastoma multiforme 系统性泛癌分析确定 DNASE2 是多形性胶质母细胞瘤的潜在预后标记和免疫治疗靶点

IF 6.8 2区医学

Genes & Diseases Pub Date : 2024-09-10 DOI: 10.1016/j.gendis.2024.101431

Jun Cao, Si Chen, Ping An, Xingqiang Wang, Xinru Xiao, Shichao Li, Ye Cheng

引用次数: 0

Oncogenic activation of PI3KCA in cancers: Emerging targeted therapies in precision oncology 癌症中 PI3KCA 的致癌激活：精准肿瘤学中的新兴靶向疗法

IF 6.8 2区医学

Genes & Diseases Pub Date : 2024-09-10 DOI: 10.1016/j.gendis.2024.101430

Yuxiang Wang, Valery Rozen, Yiqing Zhao, Zhenghe Wang

{"title":"Oncogenic activation of PI3KCA in cancers: Emerging targeted therapies in precision oncology","authors":"Yuxiang Wang, Valery Rozen, Yiqing Zhao, Zhenghe Wang","doi":"10.1016/j.gendis.2024.101430","DOIUrl":"https://doi.org/10.1016/j.gendis.2024.101430","url":null,"abstract":"Phosphoinositide 3-kinases (PI3Ks) are heterodimers consisting of a p110 catalytic subunit and a p85 regulatory subunit. The <ce:italic>PIK3CA</ce:italic> gene, which encodes the p110α, is the most frequently mutated oncogene in cancer. Oncogenic <ce:italic>PIK3CA</ce:italic> mutations activate the PI3K pathway, promote tumor initiation and development, and mediate resistance to anti-tumor treatments, making the mutant p110α an excellent target for cancer therapy. <ce:italic>PIK3CA</ce:italic> mutations occur in two hotspot regions: one in the helical domain and the other in the kinase domain. The <ce:italic>PIK3CA</ce:italic> helical and kinase domain mutations exert their oncogenic function through distinct mechanisms. For example, helical domain mutations of p110α gained direct interaction with insulin receptor substrate 1 (IRS-1) to activate the downstream signaling pathways. Moreover, p85β proteins disassociate from helical domain mutant p110α, translocate into the nucleus, and stabilize enhancer of zeste homolog 1/2 (EZH1/2). Due to the fundamental role of PI3Kα in tumor initiation and development, PI3Kα-specific inhibitors, represented by FDA-approved alpelisib, have developed rapidly in recent decades. However, side effects, including on-target side effects such as hyperglycemia, restrict the maximum dose and thus clinical efficacy of alpelisib. Therefore, developing p110α mutant-specific inhibitors to circumvent on-target side effects becomes a new direction for targeting <ce:italic>PIK3CA</ce:italic> mutant cancers. In this review, we briefly introduce the function of the PI3K pathway and discuss how <ce:italic>PIK3CA</ce:italic> mutations rewire cell signaling, metabolism, and tumor microenvironment, as well as therapeutic strategies under development to treat patients with tumors harboring a <ce:italic>PIK3CA</ce:italic> mutation.","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":null,"pages":null},"PeriodicalIF":6.8,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142258130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Arhgap29 deficiency causes EEC like syndrome in mice Arhgap29 缺乏会导致小鼠 EEC 样综合征

IF 6.8 2区医学

Genes & Diseases Pub Date : 2024-09-07 DOI: 10.1016/j.gendis.2024.101404

Dandan Chi, Yumeng Wang, Lili Yu, Wenyan Ruan, Beibei Zhang, Jian Ma, Xiaohong Duan, Yongqing Huang

引用次数: 0

Triplet therapy overcomes 3rd-EGFR TKI-resistant EGFR-L858R/T790M/C797S in trans and in cis/L718Q mutation 三联疗法可克服第三代表皮生长因子受体TKI耐药的表皮生长因子受体-L858R/T790M/C797S反式和顺式/L718Q突变

IF 6.8 2区医学

Genes & Diseases Pub Date : 2024-09-07 DOI: 10.1016/j.gendis.2024.101408

Kaibo Ding, Zhongsheng Peng, Yanjun Xu

引用次数: 0

TFE3-mediated neuroprotection: Clearance of aggregated α-synuclein and accumulated mitochondria in the AAV-α-synuclein model of Parkinson's disease TFE3 介导的神经保护：清除AAV-α-突触核蛋白帕金森病模型中聚集的α-突触核蛋白和积累的线粒体

IF 6.8 2区医学

Genes & Diseases Pub Date : 2024-09-07 DOI: 10.1016/j.gendis.2024.101429

Xin He, Mulan Chen, Yepeng Fan, Bin Wu, Zhifang Dong

{"title":"TFE3-mediated neuroprotection: Clearance of aggregated α-synuclein and accumulated mitochondria in the AAV-α-synuclein model of Parkinson's disease","authors":"Xin He, Mulan Chen, Yepeng Fan, Bin Wu, Zhifang Dong","doi":"10.1016/j.gendis.2024.101429","DOIUrl":"https://doi.org/10.1016/j.gendis.2024.101429","url":null,"abstract":"Parkinson's disease (PD) is a neurodegenerative disorder characterized by fibrillar neuronal inclusions containing aggregated α-synuclein (α-Syn). While the pathology of PD is multifaceted, the aggregation of α-Syn and mitochondrial dysfunction are well-established hallmarks in its pathogenesis. Recently, TFE3, a transcription factor, has emerged as a regulator of autophagy and metabolic processes. However, it remains unclear whether TFE3 can facilitate the degradation of α-Syn and regulate mitochondrial metabolism specifically in dopaminergic neurons. In this study, we demonstrate that TFE3 overexpression significantly mitigates the loss of dopaminergic neurons and reduces the decline in tyrosine hydroxylase-positive fiber density, thereby restoring motor function in an α-Syn overexpression model of PD. Mechanistically, TFE3 overexpression reversed α-Syn-mediated impairment of autophagy, leading to enhanced α-Syn degradation and reduced aggregation. Additionally, TFE3 overexpression inhibited α-Syn propagation. TFE3 overexpression also reversed the down-regulation of Parkin, promoting the clearance of accumulated mitochondria, and restored the expression of PGC1-α and TFAM, thereby enhancing mitochondrial biogenesis in the adeno-associated virus-α-Syn model. These findings further underscore the neuroprotective role of TFE3 in PD and provide insights into its underlying mechanisms, suggesting TFE3 as a potential therapeutic target for PD.","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":null,"pages":null},"PeriodicalIF":6.8,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142258126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Prognostic significance and multidimensional roles of interferon regulatory factors in cancer biology: A comprehensive analysis 干扰素调节因子在癌症生物学中的预后意义和多维作用：综合分析

IF 6.8 2区医学

Genes & Diseases Pub Date : 2024-09-07 DOI: 10.1016/j.gendis.2024.101426

Guo Ji, Shuyuan Xian, Jiaqi Song, Shiyu Mao, Man Pi, Qiongyi Huang, Xue Han, Jian Yin, Zan Wu, Runzhi Huang, Dongyan Han, Zhengyan Chang

引用次数: 0