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Identification of glycogene-type and validation of ST3GAL6 as a biomarker predicts clinical outcome and cancer cell invasion in urinary bladder cancer

文献类型：期刊论文

作者Dalangood, Sumiya2,3; Zhu, Zhen2; Ma, Zhihui4; Li, Jiaxuan3,4; Zeng, Qinghe2; Yan, Yilin3,4; Shen, Bing5; Yan, Jun1,6; Huang, Ruimin3,4
刊名THERANOSTICS
出版日期2020
卷号10期号:22页码:10078-10091
关键词glycogene ST3GAL6 urinary bladder cancer clinical outcome invasion
ISSN号1838-7640
DOI10.7150/thno.48711
通讯作者Yan, Jun(yan_jun@fudan.edu.cn) ; Huang, Ruimin(rmhuang@simm.ac.cn)
英文摘要Background: Urinary bladder cancer (UBC) is one of the most common causes of morbidity and mortality worldwide characterized by a high risk of invasion and metastasis; however, the molecular classification biomarkers and underlying molecular mechanisms for UBC patient stratification on clinical outcome need to be investigated. Methods: A systematic transcriptomic analysis of 185 glycogenes in the public UBC datasets with survival information and clinicopathological parameters were performed using unsupervised hierarchical clustering. The gene signature for glycogene-type classification was identified using Limma package in R language, and correlated to 8 known molecular features by Gene Set Variation Analysis (GSVA). The clinical relevance and function of a glycogene was characterized by immunohistochemistry in UBC patient samples, and quantitative RT-PCR, Western blotting, promoter activity, MAL II blotting, immunofluorescence staining, wound healing, and transwell assays in UBC cells. Results: A 14-glycogene signature for glycogene-type classification was identified. Among them, ST3GAL6, a glycotransferase to transfer sialic acid to 3'-hydroxyl group of a galactose residue, showed a significant negative association with the subtype with luminal feature in UBC patients (n=2,130 in total). Increased ST3GAL6 was positively correlated to tumor stage, grade, and survival in UBCs from public datasets or our cohort (n=52). Transcription factor GATA3, a luminal-specific marker for UBC, was further identified as a direct upstream regulator of ST3GAL6 to negatively regulate its transactivation. ST3GAL6 depletion decreased MAL II level, cell invasion and migration in 5637 and J82 UBC cells. ST3GAL6 could reverse the effects of GATA3 on global sialylation and cell invasion in SW780 cells. Conclusions: Herein, we successfully identified a novel 14-gene signature for glycogene-type classification of UBC patients. ST3GAL6 gene, from this signature, was demonstrated as a potential biomarker for poor outcomes and cell invasion in UBCs.
WOS关键词COMPREHENSIVE MOLECULAR CHARACTERIZATION ; GLYCOSYLATION ; SIALYLATION ; CONTRIBUTES ; METASTASIS ; CARCINOMA ; MIGRATION ; SUBTYPES ; TARGET ; BASAL
资助项目National Natural Science Foundation of China[81872373] ; National Natural Science Foundation of China[91859106] ; National Natural Science Foundation of China[81771890] ; National Science & Technology Major Project Key New Drug Creation and Manufacturing Program, China[2018ZX09711002010-001] ; State Key Laboratory of Drug Research[SIMM2004KF-02] ; One Hundred Talent Program of Chinese Academy of Sciences ; Wu Jieping Medical Foundation[320.6750.16051] ; Shanghai Songjiang Municipal Science and Technology Commission Natural Science Foundation[17SJKJGG10] ; Shanghai Specialized Research Fund for Integrated Chinese and Western Medicine in General Hospitals[ZHYY-ZXYJHZX-1201705]
WOS研究方向Research & Experimental Medicine
语种英语
WOS记录号WOS:000560637200003
出版者IVYSPRING INT PUBL
源URL[http://119.78.100.183/handle/2S10ELR8/292443]  
专题新药研究国家重点实验室
通讯作者Yan, Jun; Huang, Ruimin
作者单位1.Nanjing Univ, Model Anim Res Ctr, Nanjing 210061, Peoples R China
2.Nanjing Univ, MOE Key Lab Model Anim Dis Study, Model Anim Res Ctr, Nanjing 210061, Peoples R China
3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
4.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
5.Shanghai Jiao Tong Univ, Sch Med, Dept Urol, Shanghai Gen Hosp, Shanghai 200080, Peoples R China
6.Fudan Univ, Dept Lab Anim Sci, Shanghai 200032, Peoples R China
推荐引用方式
GB/T 7714		 Dalangood, Sumiya,Zhu, Zhen,Ma, Zhihui,et al. Identification of glycogene-type and validation of ST3GAL6 as a biomarker predicts clinical outcome and cancer cell invasion in urinary bladder cancer[J]. THERANOSTICS,2020,10(22):10078-10091.
APA Dalangood, Sumiya.,Zhu, Zhen.,Ma, Zhihui.,Li, Jiaxuan.,Zeng, Qinghe.,...&Huang, Ruimin.(2020).Identification of glycogene-type and validation of ST3GAL6 as a biomarker predicts clinical outcome and cancer cell invasion in urinary bladder cancer.THERANOSTICS,10(22),10078-10091.
MLA Dalangood, Sumiya,et al."Identification of glycogene-type and validation of ST3GAL6 as a biomarker predicts clinical outcome and cancer cell invasion in urinary bladder cancer".THERANOSTICS 10.22(2020):10078-10091.

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来源：上海药物研究所

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