TINF2

更新于：2025-05-07

基本信息

别名

TERF1 interacting nuclear factor 2、TERF1-interacting nuclear factor 2、TIN2

+ [2]

简介

Component of the shelterin complex (telosome) that is involved in the regulation of telomere length and protection. Shelterin associates with arrays of double-stranded TTAGGG repeats added by telomerase and protects chromosome ends; without its protective activity, telomeres are no longer hidden from the DNA damage surveillance and chromosome ends are inappropriately processed by DNA repair pathways. Plays a role in shelterin complex assembly. Isoform 1 may have additional role in tethering telomeres to the nuclear matrix.

关联

项与 TINF2 相关的药物

WO2023182899

专利挖掘

靶点

TERF1 x TINF2

作用机制

TERF1 inhibitors [+1]

在研机构

Innovabion Sp. Z O.O. [+3]

原研机构

Politechnika Gdanska [+3]

在研适应症

肿瘤

非在研适应症-

最高研发阶段药物发现

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 TINF2 相关的临床结果

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100 项与 TINF2 相关的转化医学

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0 项与 TINF2 相关的专利（医药）

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284

项与 TINF2 相关的文献（医药）

2025-04-01·Tissue and Cell

IGF2BPs-regulated TIN2 confers the malignant biological behaviors of gastric cancer cells

Article

作者: Chen, Guoqun ; Zhou, Yadong ; Huang, Da ; Liao, Zhiming ; Li, Fang ; Zhang, Ziqing

BACKGROUNDTelomere maintenance is an important feature of tumor cells. Telomeric-repeat binding factor 1 interaction nuclear protein 2 (TIN2), a key member of the shelterin proteins, functions in regulating telomere structure, length and function. Our work sought to investigate the role of TIN2 in controlling gastric cancer (GC) malignant biological behaviors.METHODSThe mRNA and protein expressions were examined by qRT-PCR, western blot and immunofluorescence assays. The relative telomerase activity and telomere length were detected using the corresponding kit and qRT-PCR, respectively. The proliferation, migration and invasion abilities were detected by CCK8 and transwell assays, respectively. Cellular oxidative stress level and Fe^2 + content were assessed by DCFH-DA staining and ELISA assays, respectively. The interaction between IGF2BP1/2/3 and TIN2 was analyzed by RIP and RNA pull down assays.RESULTSTIN2 expression was significantly increased in GC cells compared with it in gastric mucosal epithelial cells. TIN2 knockdown could impair telomerase function and induce DNA injury in GC cells. Moreover, silencing of TIN2 greatly repressed cell proliferation, metastasis, and autophagy in GC cells. Likewise, the antioxidant capacity and Fe²⁺ content were enhanced after TIN2 depletion, leading to the activation of cellular ferroptosis. In terms of mechanism, TIN2 mRNA could be recognized by IGF2BP1/2/3, and its mRNA expression and stability were decreased upon IGF2BP1/2/3 was knocked down.CONCLUSIONKnockdown of TIN2 could restrained telomerase function and the malignant abilities of proliferation, metastasis and autophagy but induced ferroptosis of GC cells, which suggested that targeting TIN2 might be a therapeutic strategy for GC.

2025-01-05·La Tunisie medicale

Prevalence of pathogenic variants of inborn errors of immunity in critically ill children admitted to the pediatric intensive care unit for sepsis: A Moroccan cohort study.

Article

作者: Jouanguy, Emmanuelle ; Aissaoui, Ouissal ; Drissi Boughanbour, Asmaa ; El Bakkouri, Jalila ; Benhsaien, Ibtihal ; Ailal, Fatima ; Casanova, Jean Laurent ; Chlilek, Abdelaziz ; Moundir, Abderrahmane ; Bousfiha, Ahmed Aziz

INTRODUCTIONPediatric sepsis remains a leading cause of morbidity and mortality in Africa. Nearly half of pediatric sepsis deaths occur in previously healthy children. The role of inborn errors of immunity (IEI) in susceptibility to sepsis is yet to be identified and their prevalence amongst previously healthy children admitted to the pediatric intensive care unit (PICU) is unclear. We aimed to assess prevalence of IEI among a cohort of children admitted to the PICU for community acquired sepsis and to describe demographic, microbiological, and genetic features of this cohort.METHODSWe listed a cohort of children admitted to our PICU for sepsis from January 2021 to March 2023. Demographic data was collected, and microbiological tests were performed. Written consent was obtained and whole exome sequencing (WES) was performed after DNA extraction.RESULTSThirty cases were included. Mean age at admission was 46 months (1-180), microorganisms were identified in 20 cases (66%). Bacterial sepsis was identified in 8 cases, viral sepsis in 6 cases and fungal sepsis in 2 cases. Mean pediatric sequential sepsis related organ failure assessment (pSOFA) score at admission was 6,46 (2-18). Mechanical ventilation was necessary in 18 cases. Inotropes were used in 17 cases and renal replacement therapy initiated in 3 cases. Pathogenic variants of IEI were identified in 5 out of 30 cases (17%). These variants were identified in the following genes BACH2, TLR7, TINF2, NFK2B and MAGT1. Overall mortality was 50% and mean intensive care unit (ICU) stay was 9,26 (1-60) days.CONCLUSIONPrevalence of pathogenic variants of IEI among children admitted to the PICU for sepsis was 17%. Our study findings support systematic screening of IEI amongst critically ill children admitted to the PICU for sepsis in order to increase our comprehension of sepsis phenotypes and improve outcomes in this group of critically ill children.

2024-12-01·Molecular Biology Reports

The expression of shelterin genes and telomere repeat analysis and their effect on Alzheimer’s disease

Article

作者: Bozkurt, Hakan ; Yılmaz, Şenay Görücü

BACKGROUNDAlzheimer's disease (AD) is an age-related dementia disorder characterized by memory loss and behavioral changes. Maintaining the integrity of telomere shortening in AD is important for cellular survival and homeostasis in all cells, especially glial cells. The shelterin protein complex provides telomere integrity. Measuring the expression levels of shelterin genes and determining the telomere lengths regulated by this complex will reveal their effects on AD progression and adult neurogenesis and will allow the detection of the disease or the determination of the progression process from an accessible tissue.METHODS AND RESULTSThe study population included 111 patients and 91 healthy controls (male and female, < 50 age). The clinical histories (age, gender, hypertension, diabetes mellitus, obesity, cardiovascular disease, MMSE, medication use, family history, sleep disorders, seizure), covariates (HGB, ESR, Na, P, Cl, BUN, CRP, B12, TSH, Glucose, and MRI findings) and the expressional changes of shelterin genes (TERF1, TERF2, TINF2, POT1, TPP1, and RAP1) between the patient and control groups were evaluated relatively. ROC analyses determined the diagnostic power of telomere repeats and gene expressions.CONCLUSIONSIn conclusion, upregulation of expression of shleterin complex genes was detected in AD, where telomeres are significantly shorter than in controls (P < 0.05). However, only TERF2 and RAP1 were significant (P < 0.05). A positive relationship was detected between telomere repeats and these genes (P < 0.05). Telomere repeats may be a strong diagnostic criterion to distinguish AD individuals from healthy individuals (AUC = 1.000). The upregulation of TERF2 and RAP1 core genes required for telomere integrity results in the instability of excessively shortened telomeres. Expression silencing of these genes may increase telomerase activity and maintain cellular survival. Also, the detection of telomere repeats has potential in the early diagnosis of AD patients.

项与 TINF2 相关的新闻（医药）

2024-08-12

·派真生物PackGene

一周要闻丨基因治疗要闻速递第115期

行业动态速览热点聚焦 01 广州首例成人重型地贫患者基因治疗成功广州市第一人民医院血液内科2024年启动了β珠蛋白生成障碍性贫血（以下简称“β地贫”）的基因治疗临床研究，为广州市首位成人重型β地贫患者进行了基因治疗，嘉嘉从此摆脱输血依赖。目前，基因治疗在国际上也逐渐成为“一次治疗永久性治愈”的β地贫的新疗法。推荐阅读：广州首例成人重型地贫患者基因治疗成功 02 凌意生物AAV基因药物LY-M003获FDA孤儿药及儿科罕见病资格认定 2024年8月7日，凌意（杭州）生物科技有限公司（以下简称“凌意生物”）宣布，其自主研发的基因治疗药物LY-M003注射液获美国FDA孤儿药（Orphan-drug designation, ODD）资格认定，用于治疗肝豆状核变性（Wilson’s disease，WD）。推荐阅读：凌意生物AAV基因药物LY-M003获FDA孤儿药及儿科罕见病资格认定 03 DMD疗法显著改善疾病指标，将与FDA讨论加速批准途径近日，Avidity Biosciences宣布，在研抗体偶联寡核苷酸疗法delpacibart zotadirsen（del-zota），在适合接受外显子44跳跃疗法治疗的杜氏肌营养不良症（DMD44）患者中进行的1/2期临床试验EXPLORE44中获得积极数据。Del-zota显著提高患者抗肌萎缩蛋白的生产，最高达到了正常水平的54%。此外，del-zota使肌酸激酶水平下降至接近正常水平，与基线相比减少超过80%。Avidity公司表示，将与美国FDA展开讨论，寻求加速批准这一疗法的最佳途径。推荐阅读：DMD疗法显著改善疾病指标，将与FDA讨论加速批准途径 04 瑞金医院成功完成针对帕金森病AAV基因药物临床研究的上海首例受试者给药由上海交通大学医学院附属瑞金医院（以下简称“瑞金医院”）发起的一项“BBM-P002注射液立体定向双侧壳核治疗中晚期原发性帕金森病的安全性、耐受性和有效性的研究”，近期顺利完成上海首例受试者给药。推荐阅读：瑞金医院成功完成针对帕金森病AAV基因药物临床研究的上海首例受试者给药创新突破 01 Nature子刊：阿尔茨海默病新发现，不止神经元，胶质细胞也产生Aβ毒蛋白并促进斑块形成 2024年8月5日，马克斯·普朗克多学科科学研究所的研究人员在 Nature 子刊 Nature Neuroscience 上发表了题为：Oligodendrocytes produce amyloid-β and contribute to plaque formation alongside neurons in Alzheimer’s disease model mice 的研究论文。这项研究表明，除了神经元，大脑中的一种特殊神经胶质细胞——少突胶质细胞，也会产生β-淀粉样蛋白（Aβ）并于神经元一起促进斑块形成，这一发现可能会为未来的阿尔茨海默病治疗开辟新途径。推荐阅读： Nature子刊：阿尔茨海默病新发现，不止神经元，胶质细胞也产生Aβ毒蛋白并促进斑块形成 02 Nature：肝脏“免疫变阻器”，抑制慢性乙肝病毒感染中的CD8+T细胞免疫近日，德国慕尼黑工业大学的研究人员在国际顶尖学术期刊 Nature 上发表了题为：A liver immune rheostat regulates CD8 T cell immunity in chronic HBV infection 的研究论文。该研究证明了肝窦内皮细胞作为肝脏“免疫变阻器”，使HBV病毒特异性CD8+T细胞难以被激活，并导致其效应功能丧失，而通过靶向抑制性的腺苷酸环化酶-cAMP-PKA信号轴来调节肝脏“免疫变阻器”功能，有望提高旨在重建慢性HBV感染中HBV特异性CD8+T细胞反应的治疗方法的效果。推荐阅读：Nature：肝脏“免疫变阻器”，抑制慢性乙肝病毒感染中的CD8+T细胞免疫 03 Mol Cancer | 西南医科大学姜鲜/章卓合作揭示miRNA在肝细胞癌中高表达的调节通路 2024年8月6日，西南医科大学姜鲜及章卓共同通讯在 Molecular Cancer（IF=28）在线发表题为 “Circular RNA ACVR2A promotes the progression of hepatocellular carcinoma through mir-511-5p targeting PI3K-Akt signaling pathway” 的研究论文。该研究发现circACVR2A可以直接与miR511-5p相互作用，作为miRNA海绵调节PI3K-Akt信号通路中相关蛋白的表达。推荐阅读：Mol Cancer | 西南医科大学姜鲜/章卓合作揭示miRNA在肝细胞癌中高表达的调节通路 04 CDD | 上海交通大学韦芳/许迅等团队合作发现糖尿病视网膜病的潜在治疗新靶点 2024年7月30日，上海交通大学韦芳、许迅及Li Huiming共同通讯在Cell Death & Differentiation 在线发表题为”TIN2 modulates FOXO1 mitochondrial shuttling to enhance oxidative stress-induced apoptosis in retinal pigment epithelium under hyperglycemia“的研究论文，该研究在体内和体外实验中，观察到氧化应激诱导的RPE细胞凋亡显著增加，同时端粒蛋白TIN2的表达也较高。深入研究证实高糖诱导的线粒体定位的TIN2的升高损害线粒体活性，削弱内在的抗氧化防御，从而导致线粒体依赖的凋亡途径的激活。推荐阅读：CDD | 上海交通大学韦芳/许迅等团队合作发现糖尿病视网膜病的潜在治疗新靶点资本速递 01 正序生物完成超亿元A+轮融资，开发新型基因编辑疗法近日，正序生物宣布完成超亿元人民币的A+轮融资。本轮融资由上海国投孚腾资本领投，联新资本、博裕资本、礼来亚洲基金、万物资本、红杉中国等现有股东跟投。根据正序生物新闻稿，本轮融资将进一步加速CS-101临床研究和商业化推进，并支持体内治疗管线的临床转化，推动全球化布局和基因编辑产品早日上市。推荐阅读：正序生物完成超亿元A+轮融资，开发新型基因编辑疗法 02 近20亿美元！罗氏布局阿尔兹海默病基因疗法 8月6日，专注于基因治疗药物公司Sangamo Therapeutics, Inc.(纳斯达克股票代码:SGMO)宣布，公司已经与罗氏集团旗下公司基因泰克达成许可协议，开发静脉注射基因组药物来治疗包括阿尔兹海默病的神经退行性疾病。推荐阅读：近20亿美元！罗氏布局阿尔兹海默病基因疗法 03 19.5亿美元！罗氏与Sangamo合作开发基因组学药物 8月6日，Sangamo Therapeutics宣布已与罗氏旗下公司基因泰克达成许可协议，合作开发静脉注射基因组学药物以治疗某些神经退行性疾病。推荐阅读：19.5亿美元！罗氏与Sangamo合作开发基因组学药物参考资料： https://mp.weixin.qq.com/s/UGha80WGgkLmlVRWAtTj1A https://mp.weixin.qq.com/s/VV5ClKQR2LCax7N7GKsBCQ https://mp.weixin.qq.com/s/KfBGg2qJArysD-xaFRwK7Q https://mp.weixin.qq.com/s/QwUr0BnZEg7a544GCnBLBQ https://mp.weixin.qq.com/s/tsnhtLXwn8OAWYRBpsqdtw https://mp.weixin.qq.com/s/43yp-CkViucSU0uqa0L6CQ https://mp.weixin.qq.com/s/I4SJdbNHgqPsoiTddtPHaQ https://mp.weixin.qq.com/s/sEYkbIzwbZr4huRsosGQIQ https://mp.weixin.qq.com/s/eVXpNzsYz9q1cSQRY8_0Ng https://mp.weixin.qq.com/s/UQIoC-foQdfXnK_eEh8HPA https://mp.weixin.qq.com/s/1i67X-PxBVX6mX4ks11t5w 关于派真生物

孤儿药基因疗法寡核苷酸加速审批临床研究