更新于：2024-11-01

GALNT5

更新于：2024-11-01

基本信息

别名

GalNAc-T5、GALNT5、Polypeptide GalNAc transferase 5

+ [4]

简介

Catalyzes the initial reaction in O-linked oligosaccharide biosynthesis, the transfer of an N-acetyl-D-galactosamine residue to a serine or threonine residue on the protein receptor. Has activity toward EA2 peptide substrate, but has a weak activity toward Muc2 or Muc1b substrates (By similarity).

关联

100 项与 GALNT5 相关的临床结果

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100 项与 GALNT5 相关的转化医学

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0 项与 GALNT5 相关的专利（医药）

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项与 GALNT5 相关的文献（医药）

2024-11-01·International Journal of Biological Macromolecules

Overexpression of sialyl Lewisa carrying mucin-type glycoprotein in prostate cancer cell line contributes to aggressiveness and metastasis

Article

作者: Chachadi, Vishwanath B. ; Gurav, Maruti J. ; Manasa, J. ; Sanji, Ashwini S. ; Gurav, Maruti J ; Chachadi, Vishwanath B ; Sanji, Ashwini S ; Kennedy, John F ; J, Manasa ; Vanti, Gulamnabi ; Megalamani, Prasanna H ; Kurjogi, Mahantesh ; Megalamani, Prasanna H. ; Kennedy, John F. ; Kaulgud, Ram

Metastasis-promoting Lewis and sialyl Lewis antigens expressed on glycoproteins such as mucins are frequently displayed on the surface of prostate cancer cells and could thus be ideal candidates as measures of prostate cancer aggressiveness. The current study describes the altered expression of sialyl Lewis^a (sLe^a) antigen attached to glycoproteins and key glycosyltransferases between normal prostate (RWPE-1) and cancerous cell lines (LNCaP and DU145). Our results suggest that the expression of sLe^a on different glycoproteins correlates with the aggressiveness of prostate cancer cells, as determined by flow cytometry and fluorescence microscopy. Blotting studies revealed that sLe^a-bearing glycoproteins, similar to mucins, are predominantly expressed in the more aggressive DU145 cells, followed by LNCaP cells. Immunohistochemistry technique showed a gradient of sLe^a expression, with low levels in low-grade prostate cancer (stage II/III) and increasing levels in high-grade cancer (stage IV), indicating its potential as a prognostic marker. Additionally, in qRT-PCR analysis significant upregulation of the glycosyltransferases GALNT5 and ST3GAL6 was observed, correlating with the increased sLe^a expression in LNCaP (3.2- and 14.5-fold) and DU145 (3.3- and 23.75-fold) cells. Our data indicates a correlation between sLe^a selectin ligand expression and prostate cancer aggressiveness. Furthermore, GALNT5 and ST3GAL6 could serve as benchmarks in PCa malignancy.

2023-07-01·Gene

Identifying novel risk conferring genes involved in glycosylation processes with familial schizophrenia in an Indian cohort: Prediction of ADAMTS9 gene variant for structural stability

Article

作者: Das, Dhanjit Kumar ; Menon, Shyla ; Shekhar, Bipin Raj ; Khare, Satyajeet P. ; Nayak, Ajita Sunil ; Rupani, Karishma ; Kumbhar, Bajarang Vasant ; Parkar, Shubhangi Raghunath ; Gawde, Harshavardhan

Schizophrenia is a complex neuropsychiatric disorder and heritability is as high as 80 % making it the most heritable mental disorder. Although GWAS has identified numerous variants, the pathophysiology is still elusive. Here, an attempt was made to identify genetic risk factors in familial cases of schizophrenia that are associated with a common causative pathway. To achieve this objective, exome sequencing was done in 4 familial cases and identified six unique coding variants in five genes. Among these genes, PIGQ gene has two pathogenic variants, one nonsense and in-frame deletion. One missense variant in GALNT16 and one in GALNT5 have variable damaging score, however, the other variants, in ADAMTS9 and in LTBP4 have the highest damaging score. Further analysis showed that the variant of LTBP4 was not present in the functional domain. The other missense variant in the ADAMTS9 gene was found to be significant and was present in the thrombospondin repeat motif, one of the important motifs. Detailed molecular dynamics simulation study on this variant showed a damaging effect on structural stability. Since, all these genes culminated into the glycosylation process, it was evident that an aberrant glycosylation process may be one of the risk factors. Although, extracellular matrix formation through glycosylation have been shown to be associated, the involvement of ADAMTS9 and PIGQ gene mediated glycosylation has not been reported. In this paper, a novel link between ADAMTS9 and PIGQ gene with schizophrenia have been reported. Therefore, this novel observation has contributed immensely to the existing knowledge on risk factor of Schizophrenia.

2023-05-01·International Wound Journal

Bioinformatics analysis and identification of dysregulated POSTN in the pathogenesis of keloid

Article

作者: Hu, Zhicheng ; Xu, Hailin ; Wang, Zhiyong ; Zhu, Jiayuan ; Yang, Hao

AbstractKeloid is a benign fibro‐proliferative dermal tumour formed by an abnormal scarring response to injury and characterised by excessive collagen accumulation and invasive growth. The pathophysiology of keloids is complex, and the treatment for keloids is still an unmet medical need. Here, we investigated the transcriptional gene that influences keloid development by comparing keloid, non‐lesioned keloid skin and normal skin as well as keloid fibroblast and normal fibroblast (GSE83286, GSE92566, GSE44270). Based on the analysis, 146 up‐regulated genes and 48 down‐regulated genes were found in keloid tissue compared with normal skin and keloid no‐lesioned skin. Eleven genes were further identified by overlapping the DEGs from keloid tissue described previously with DEGs in keloid fibroblast. The overlapped genes included PRR16, SFRP2, EDIL3, GERM1, POSTN, PDE3A, GALNT5, F2RL2, EYA4, ZFHX4, and AIM2. POSTN is the most crucial node in PPI network, which mainly correlate to collagen‐related genes. Moreover, siRNA knockdown identified POSTN is a crucial regulatory gene that regulates keloid fibroblast migration and collagen I, collagen III expression level. In conclusion, our study identified 11 hub genes that play crucial role in keloid formation and provided insights for POSTN to be the therapeutic target for keloid through bioinformatic analysis of three datasets. Additionally, our results would support the development of future therapeutic strategies.

项与 GALNT5 相关的新闻（医药）

2024-10-22

·今日头条

改善耐药！上海交通大学发文：胰腺癌患者的潜在治疗靶点

【导读】化疗耐药是胰腺导管腺癌(PDAC)治疗中的一大挑战。PDAC的一线化疗方案包括基于吉西他滨的方案，如AG方案，氟尿嘧啶基方案，如FOLFIRINOX方案(5-氟尿嘧啶5-FU，奥沙利铂，伊立替康)以及针对BRCA突变患者的铂类基方案。人们已经做了大量研究来探索吉西他滨基和铂类基方案耐药的机制，但在FOLFIRINOX方案耐药的机制方面却鲜有研究。 10月21日，上海交通大学研究团队在期刊《Cell Death&Disease》上发表了研究论文，题为“Oncogenic GALNT5 confers FOLFIRINOX resistance via activating the MYH9/ NOTCH/ DDR axis in pancreatic ductal adenocarcinoma”，本研究中，研究人员将GALNT5确定为FOLFIRINOX方案耐药的重要调节因子和潜在的治疗靶点。通过克隆形成试验和流式细胞术，研究人员探究了GALNT5在PDAC细胞增殖和凋亡中的作用。通过RNA-seq和GSEA（基因集富集分析），研究人员揭示了潜在的机制。通过蛋白质免疫印迹实验、实时PCR和免疫荧光，验证了相关途径。研究人员建立了小鼠原位异种移植PDAC模型，以在体内研究GALNT5的功能。GALNT5在PDAC组织中高度表达，并预测PDAC患者的预后不良。PDAC细胞中GALNT5的上调通过抑制DNA损伤，赋予了PDAC对FOLFIRINOX的耐药性。此外，GALNT5与MYH9相互作用，参与NOTCH通路的激活，从而阻碍FOI引起的DNA损伤。在体内验证了GALNT5促进FOLFIRINOX耐药的功能。在这项研究中，研究人员发现在PDAC中异常高表达的GALNT5通过与MYH9相互作用，参与激活NOTCH通路，从而抑制DDR，达到对FOLFIRINOX耐药的目的，并导致不良预后。研究人员发现GALNT5可能是对FOLFIRINOX化疗产生耐药性的PDAC患者的一个潜在治疗靶点。 https://www-nature-com.libproxy1.nus.edu.sg/articles/s41419-024-07110-w#Abs1 背景信息 01 胰腺癌是恶性程度最高的肿瘤之一，在中国恶性肿瘤发病率中排名第8位，是全球第7大癌症致死原因，预计在未来20年中，胰腺导管腺癌将成为第二大癌症致死原因。胰腺癌的传统治疗方法主要包括手术切除、化疗和放疗。对于可切除的胰腺癌，手术是首选的治疗方案。然而，胰腺癌病例往往在早期就伴有淋巴结转移或远处器官转移，当时仅有不到20%的患者有机会接受手术治疗。对于边界可切除（BR）和局部晚期（LA）胰腺癌，通过化疗等手段将其转化为可切除的胰腺癌，以争取手术治疗是目标。对于无法通过手术切除的胰腺癌，目前主要的治疗方法是化疗和放疗。目前，胰腺癌的一线化疗方案主要包括以吉西他滨为基础的方案，如AG（白蛋白紫杉醇和吉西他滨），以及以氟尿嘧啶为基础的方案，如FOLFIRINOX（5-氟尿嘧啶、奥沙利铂和伊立替康）。自2003年以来，FOLFIRINOX方案首次在晚期胰腺癌患者中进行临床研究。随着大量研究结果的出现，近年来NCCN指南已将FOLFIRINOX方案推荐为局部晚期和转移性胰腺癌的标准一线化疗方案。ASCO 2018年报告的修改后的FOLFIRINOX与吉西他滨辅助化疗在胰腺癌切除术后的对比研究结果，进一步将这种三药联合化疗方案扩展至术后辅助化疗。新NCCN指南进一步将FOLFIRINOX方案推荐为体能状况良好的患者的一线辅助化疗选择。化疗干预有效地改善了胰腺癌手术的预后和患者的生存率。此外，许多研究报告称，在进行胰腺癌切除的患者中，FOLFIRINOX方案的生存期显著长于吉西他滨，但它必须面对频繁出现的药物耐药问题。目前正在加强对吉西他滨耐药机制的研究，但对于其他一线化疗方案如FOLFIRINOX的耐药机制的研究却很少。 GALNT5在体内化学耐药中的作用的验证 02 为了研究GALNT5在体内对FOI抵抗的作用，研究人员采用KPC1199细胞建立小鼠原位异种移植PDAC模型。KPC1199细胞来源于KPC小鼠模型，该模型含有K-rasLSL.G12D/+；和Trp53R172H/+，因此恢复了PDAC的常见基因突变。通过生物荧光成像来评估体内治疗组与对照组肿瘤体积的变化差异。研究人员测量了总荧光强度，发现在sh-GALNT5组中，荧光强度降低更多，这表明GALNT5的敲低使PDAC细胞对FOI更敏感。此外，研究人员取出异位移植肿瘤并对其进行分析，发现在FOI治疗组中，sh-GALNT5组的肿瘤生长抑制效果比sh-Ctrl组更强。小鼠PDX胰腺癌模型的体积和重量分析也得到了与原位异位移植模型相同的结果。研究人员进一步对PDX模型样本进行了HE染色和组织化学染色，结果显示：在未处理组中，PDX组织的分化程度最低。单独使用FOI治疗或GALNT5敲低均可改善PDX组织的分化程度，同时进行FOI治疗和GALNT5敲低的FOI-ShGALNT5组分化程度最高。PDX组织中P-ATM（Ser1981）染色反映的DNA损伤趋势与HE染色一致。PDX肿瘤的生长趋势也与NICD、Ki67和CK19的组织化学染色变化一致。这些结果表明，GALNT5敲低和FOI治疗对抑制胰腺癌的生长和分化有协同作用，提示GALNT5敲低可增强胰腺癌细胞对FOLFIRINOX化疗的敏感性。体外实验表明，GALNT5高表达会增强胰腺癌细胞对FOLFIRINOX化疗的敏感性 GALNT5-MYH9-NICD相互作用在体内对化疗耐药的验证 03 为了在体内验证GALNT5-MYH9-NICD轴的相互作用，研究人员使用了与上述实验相同的小鼠KPC1199细胞异位移植肿瘤模型和小鼠胰腺癌PXD模型，所有模型每周接受一次FOI治疗以恢复临床给药状态。结果表明，在FOI治疗的背景下，与对照组相比，过表达GALNT5后肿瘤明显增大，而持续敲低MYH9后肿瘤生长明显受到抑制。这一趋势在注射小鼠VPA后逆转。研究人员在小鼠体内成像结果、异位移植肿瘤体重统计数据和PXD模型的肿瘤体积和重量统计数据（第35天）中也发现了同样的趋势。对PXD模型进行取样后进行了HE染色和免疫组织化学染色，观察到：在OV-Vector组中，接受FOI治疗后分化程度最佳，而GALNT5在肿瘤内的过表达导致PDX组织的分化程度显著降低，而MYH9在肿瘤内的下调又使PDX组织的分化程度再次增加。最后，VPA的腹腔注射使分化趋势得以恢复。PDX组织中P-ATM（Ser1981）染色反映的DNA损伤趋势与HE染色反映的趋势一致。PDX肿瘤的生长趋势（通过NICD、Ki67和CK19的组织化学染色变化反映）也与上述结果一致。结合之前的体外实验结果，研究人员推测GALNT5通过与MYH9结合并在体内抑制NOTCH信号通路，从而赋予胰腺癌细胞对FOLFIRINOX化疗的耐药性。【参考资料】 https://www-nature-com.libproxy1.nus.edu.sg/articles/s41419-024-07110-w#Abs1 【关于投稿】转化医学网（360zhyx.com）是转化医学核心门户，旨在推动基础研究、临床诊疗和产业的发展，核心内容涵盖组学、检验、免疫、肿瘤、心血管、糖尿病等。如您有最新的研究内容发表，欢迎联系我们进行免费报道（公众号菜单栏-在线客服联系），我们的理念：内容创造价值，转化铸就未来！转化医学网（360zhyx.com）发布的文章旨在介绍前沿医学研究进展，不能作为治疗方案使用；如需获得健康指导，请至正规医院就诊。热门推荐活动点击免费报名 🕓 线上｜10月22日 ▶ 代谢组学在精准医学方向的研究应用线上高峰论坛 🕓 上海｜11月15日-16日 ▶ 2024第一届中国类器官转化医学大会 🕓 上海｜11月21日-24日 ▶ 第七届上海国际肿瘤内科学论坛 🕓 全国｜2024年12月-2025年03月 ▶ 中国转化医学产业大会点击对应文字查看详情

放射疗法临床结果