中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
首页 机构 成果 学者
  
  1. CAS IR Grid
  2. 上海药物研究所
  3. 中国科学院上海药物研究所
Integrative analysis of the ST6GALNAC family identifies GATA2-upregulated ST6GALNAC5 as an adverse prognostic biomarker promoting prostate cancer cell invasion

文献类型：期刊论文

作者Li, Meiqian1; Ma, Zhihui2,3; Zhang, Yuqing4; Feng, Hanyi5; Li, Yang4; Sang, Weicong4; Zhu, Rujian4; Huang, Ruimin2,3,5; Yan, Jun4,6,7
刊名CANCER CELL INTERNATIONAL
出版日期2023-07-19
卷号23期号:1页码:19
关键词Prostate cancer Metastasis ST6GALNAC5 GATA2 Prognostic biomarker
DOI10.1186/s12935-023-02983-x
通讯作者Zhu, Rujian(tzzhurj@163.com) ; Huang, Ruimin(rmhuang@simm.ac.cn) ; Yan, Jun(yan_jun@fudan.edu.cn)
英文摘要BackgroundST6GALNAC family members function as sialyltransferases and have been implicated in cancer progression. However, their aberrant expression levels, prognostic values and specific roles in metastatic prostate cancer (PCa) remain largely unclear.MethodsTwo independent public datasets (TCGA-PRAD and GSE21032), containing 648 PCa samples in total, were employed to comprehensively examine the mRNA expression changes of ST6GALNAC family members in PCa, as well as their associations with clinicopathological parameters and prognosis. The dysregulation of ST6GALNAC5 was further validated in a mouse PCa model and human PCa samples from our cohort (n = 64) by immunohistochemistry (IHC). Gene Set Enrichment Analysis, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes and drug sensitivity analyses were performed to enrich the biological processes most related to ST6GALNAC5. Sulforhodamine B, transwell, luciferase reporter and chromatin immunoprecipitation (ChIP) assays were used to examine the PCa cell proliferation, invasion and transcriptional regulation, respectively.ResultsSystematical investigation of six ST6GALNAC family members in public datasets revealed that ST6GALNAC5 was the only gene consistently and significantly upregulated in metastatic PCa, and ST6GALNAC5 overexpression was also positively associated with Gleason score and predicted poor prognosis in PCa patients. IHC results showed that (1) ST6GALNAC5 protein expression was increased in prostatic intraepithelial neoplasia and further elevated in PCa from a PbCre;Pten(F/F) mouse model; (2) overexpressed ST6GALNAC5 protein was confirmed in human PCa samples comparing with benign prostatic hyperplasia samples from our cohort (p < 0.001); (3) ST6GALNAC5 overexpression was significantly correlated with perineural invasion of PCa. Moreover, we first found transcription factor GATA2 positively and directly regulated ST6GALNAC5 expression at transcriptional level. ST6GALNAC5 overexpression could partially reverse GATA2-depletion-induced inhibition of PCa cell invasion. The GATA2-ST6GALNAC5 signature exhibited better prediction on the poor prognosis in PCa patients than GATA2 or ST6GALNAC5 alone.ConclusionsOur results indicated that GATA2-upregulated ST6GALNAC5 might serve as an adverse prognostic biomarker promoting prostate cancer cell invasion.
WOS关键词PERINEURAL INVASION ; TRANSCRIPTION FACTORS ; EXPRESSION ; METASTASIS ; GENE ; SIALYLTRANSFERASE ; GANGLIOSIDE ; MULTIPLE ; SURVIVAL ; ST3GAL6
WOS研究方向Oncology
语种英语
出版者BMC
WOS记录号WOS:001032067600001
源URL[http://119.78.100.183/handle/2S10ELR8/306457]  
专题中国科学院上海药物研究所
通讯作者Zhu, Rujian; Huang, Ruimin; Yan, Jun
作者单位1.Nanjing Univ, Med Sch, Model Anim Res Ctr, Nanjing, Peoples R China
2.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Drug Safety Evaluat & Res, Shanghai, Peoples R China
3.Univ Chinese Acad Sci, Beijing, Peoples R China
4.Fudan Univ, Shanghai Pudong Hosp, Dept Urol, Pudong Med Ctr, Shanghai, Peoples R China
5.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing, Peoples R China
6.Fudan Univ, Dept Lab Anim Sci, Shanghai, Peoples R China
7.Nanjing Univ, Model Anim Res Ctr, Nanjing, Peoples R China
推荐引用方式
GB/T 7714		 Li, Meiqian,Ma, Zhihui,Zhang, Yuqing,et al. Integrative analysis of the ST6GALNAC family identifies GATA2-upregulated ST6GALNAC5 as an adverse prognostic biomarker promoting prostate cancer cell invasion[J]. CANCER CELL INTERNATIONAL,2023,23(1):19.
APA Li, Meiqian.,Ma, Zhihui.,Zhang, Yuqing.,Feng, Hanyi.,Li, Yang.,...&Yan, Jun.(2023).Integrative analysis of the ST6GALNAC family identifies GATA2-upregulated ST6GALNAC5 as an adverse prognostic biomarker promoting prostate cancer cell invasion.CANCER CELL INTERNATIONAL,23(1),19.
MLA Li, Meiqian,et al."Integrative analysis of the ST6GALNAC family identifies GATA2-upregulated ST6GALNAC5 as an adverse prognostic biomarker promoting prostate cancer cell invasion".CANCER CELL INTERNATIONAL 23.1(2023):19.

入库方式： OAI收割

来源：上海药物研究所

浏览0
下载0
收藏0
其他版本

除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。