Upregulation of NDRG1 predicts poor outcome and facilitates disease progression by influencing the EMT process in bladder cancer

N-myc downstream regulated gene 1 (NDRG1) is an intracellular protein involved in cell differentiation and was recently reported to exert various effects in several cancers. However, its expression and role in bladder cancer remain unclear. Our study enrolled 100 bladder cancer patients to detect ND...

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Veröffentlicht in:Scientific reports 2019-03, Vol.9 (1), p.5166-5166, Article 5166
Hauptverfasser: Li, Aiwei, Zhu, Xi, Wang, Chanjuan, Yang, Shuo, Qiao, Yan, Qiao, Rui, Zhang, Jie
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Zhu, Xi
Wang, Chanjuan
Yang, Shuo
Qiao, Yan
Qiao, Rui
Zhang, Jie
description N-myc downstream regulated gene 1 (NDRG1) is an intracellular protein involved in cell differentiation and was recently reported to exert various effects in several cancers. However, its expression and role in bladder cancer remain unclear. Our study enrolled 100 bladder cancer patients to detect NDRG1 expression in tumour tissues by immunohistochemistry. Correlations between NDRG1 expression and clinical factors were analysed. An NDRG1 overexpression plasmid and NDRG1 siRNAs were transfected into bladder cancer cell lines. Cell biological behaviours were assessed by CCK-8, flow cytometry, wound healing and Transwell assays. Additionally, the influence of NDRG1 on epithelial-mesenchymal transition (EMT) was investigated by western blotting and real-time PCR. NDRG1 expression in urine from bladder cancer patients was examined by ELISA. NDRG1 protein levels were significantly increased in bladder cancer patients and correlated with tumour stage (p = 0.025), lymph node metastasis (p = 0.034) and overall survival (p = 0.016). Patients with high NDRG1 expression had poorer outcomes than those with low NDRG1 expression. NDRG1 overexpression was associated with increased cell proliferation, migration, and invasion and decreased apoptotic cell numbers; NDRG1 knockdown resulted in the inverse effects. Moreover, upregulated NDRG1 expression was associated with downregulated Cytokeratin 7 and Claudin-1 expression and upregulated N-cad, β-catenin and slug expression. Downregulated NDRG1 expression was associated with the inverse effects. Urine protein levels could distinguish bladder cancer patients from healthy controls, with an area under the curve of 0.909. NDRG1 promoted EMT in bladder cancer and could be an effective diagnostic and prognostic biomarker in bladder cancer patients.
doi_str_mv 10.1038/s41598-019-41660-w
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However, its expression and role in bladder cancer remain unclear. Our study enrolled 100 bladder cancer patients to detect NDRG1 expression in tumour tissues by immunohistochemistry. Correlations between NDRG1 expression and clinical factors were analysed. An NDRG1 overexpression plasmid and NDRG1 siRNAs were transfected into bladder cancer cell lines. Cell biological behaviours were assessed by CCK-8, flow cytometry, wound healing and Transwell assays. Additionally, the influence of NDRG1 on epithelial-mesenchymal transition (EMT) was investigated by western blotting and real-time PCR. NDRG1 expression in urine from bladder cancer patients was examined by ELISA. NDRG1 protein levels were significantly increased in bladder cancer patients and correlated with tumour stage (p = 0.025), lymph node metastasis (p = 0.034) and overall survival (p = 0.016). Patients with high NDRG1 expression had poorer outcomes than those with low NDRG1 expression. NDRG1 overexpression was associated with increased cell proliferation, migration, and invasion and decreased apoptotic cell numbers; NDRG1 knockdown resulted in the inverse effects. Moreover, upregulated NDRG1 expression was associated with downregulated Cytokeratin 7 and Claudin-1 expression and upregulated N-cad, β-catenin and slug expression. Downregulated NDRG1 expression was associated with the inverse effects. Urine protein levels could distinguish bladder cancer patients from healthy controls, with an area under the curve of 0.909. 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However, its expression and role in bladder cancer remain unclear. Our study enrolled 100 bladder cancer patients to detect NDRG1 expression in tumour tissues by immunohistochemistry. Correlations between NDRG1 expression and clinical factors were analysed. An NDRG1 overexpression plasmid and NDRG1 siRNAs were transfected into bladder cancer cell lines. Cell biological behaviours were assessed by CCK-8, flow cytometry, wound healing and Transwell assays. Additionally, the influence of NDRG1 on epithelial-mesenchymal transition (EMT) was investigated by western blotting and real-time PCR. NDRG1 expression in urine from bladder cancer patients was examined by ELISA. NDRG1 protein levels were significantly increased in bladder cancer patients and correlated with tumour stage (p = 0.025), lymph node metastasis (p = 0.034) and overall survival (p = 0.016). Patients with high NDRG1 expression had poorer outcomes than those with low NDRG1 expression. 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Li, Aiwei</au><au>Zhu, Xi</au><au>Wang, Chanjuan</au><au>Yang, Shuo</au><au>Qiao, Yan</au><au>Qiao, Rui</au><au>Zhang, Jie</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Upregulation of NDRG1 predicts poor outcome and facilitates disease progression by influencing the EMT process in bladder cancer</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2019-03-26</date><risdate>2019</risdate><volume>9</volume><issue>1</issue><spage>5166</spage><epage>5166</epage><pages>5166-5166</pages><artnum>5166</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>N-myc downstream regulated gene 1 (NDRG1) is an intracellular protein involved in cell differentiation and was recently reported to exert various effects in several cancers. However, its expression and role in bladder cancer remain unclear. Our study enrolled 100 bladder cancer patients to detect NDRG1 expression in tumour tissues by immunohistochemistry. Correlations between NDRG1 expression and clinical factors were analysed. An NDRG1 overexpression plasmid and NDRG1 siRNAs were transfected into bladder cancer cell lines. Cell biological behaviours were assessed by CCK-8, flow cytometry, wound healing and Transwell assays. Additionally, the influence of NDRG1 on epithelial-mesenchymal transition (EMT) was investigated by western blotting and real-time PCR. NDRG1 expression in urine from bladder cancer patients was examined by ELISA. NDRG1 protein levels were significantly increased in bladder cancer patients and correlated with tumour stage (p = 0.025), lymph node metastasis (p = 0.034) and overall survival (p = 0.016). Patients with high NDRG1 expression had poorer outcomes than those with low NDRG1 expression. NDRG1 overexpression was associated with increased cell proliferation, migration, and invasion and decreased apoptotic cell numbers; NDRG1 knockdown resulted in the inverse effects. Moreover, upregulated NDRG1 expression was associated with downregulated Cytokeratin 7 and Claudin-1 expression and upregulated N-cad, β-catenin and slug expression. Downregulated NDRG1 expression was associated with the inverse effects. Urine protein levels could distinguish bladder cancer patients from healthy controls, with an area under the curve of 0.909. NDRG1 promoted EMT in bladder cancer and could be an effective diagnostic and prognostic biomarker in bladder cancer patients.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>30914736</pmid><doi>10.1038/s41598-019-41660-w</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0003-1079-7511</orcidid><oa>free_for_read</oa></addata></record>
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subjects 13
13/1
13/109
13/2
13/31
13/51
13/89
38
38/77
631/67/1857
631/67/589/1336
631/80/84/2176
82
Apoptosis
Apoptosis - genetics
Bladder cancer
Cancer
Case-Control Studies
Cell Cycle Proteins - genetics
Cell Cycle Proteins - metabolism
Cell Cycle Proteins - urine
Cell differentiation
Cell Line, Tumor
Cell migration
Cell Movement - genetics
Cell proliferation
Cell Proliferation - genetics
Cell Survival - genetics
Cholecystokinin
Cytokeratin
Disease Progression
Enzyme-linked immunosorbent assay
Epithelial-Mesenchymal Transition - genetics
Female
Flow cytometry
Gene Expression Regulation, Neoplastic
Health risk assessment
Humanities and Social Sciences
Humans
Immunohistochemistry
Intracellular Signaling Peptides and Proteins - genetics
Intracellular Signaling Peptides and Proteins - metabolism
Intracellular Signaling Peptides and Proteins - urine
Lymph nodes
Male
Mesenchyme
Metastases
Middle Aged
multidisciplinary
Myc protein
Prognosis
Proteins
RNA, Messenger - genetics
RNA, Messenger - metabolism
Science
Science (multidisciplinary)
siRNA
Treatment Outcome
Tumor cell lines
Tumors
Up-Regulation - genetics
Urinary Bladder Neoplasms - diagnosis
Urinary Bladder Neoplasms - genetics
Urinary Bladder Neoplasms - pathology
Urinary Bladder Neoplasms - urine
Urine
Western blotting
Wound healing
β-Catenin
title Upregulation of NDRG1 predicts poor outcome and facilitates disease progression by influencing the EMT process in bladder cancer
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