The enhanced expression of estrogen‐related receptor α in human bladder cancer tissues and the effects of estrogen‐related receptor α knockdown on bladder cancer cells

Estrogen‐related receptor α (ERRα) belongs to the superfamily of nuclear orphan receptors. However, the role of ERRα in bladder cancer remains unknown. This study examined the expression of ERRα in bladder cancer tissues and explored the molecular mechanisms of ERRα in bladder cancer progression. Th...

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Veröffentlicht in:Journal of cellular biochemistry 2019-08, Vol.120 (8), p.13841-13852
Hauptverfasser: Ye, Xinqing, Guo, Jinan, Zhang, Hongxiang, Meng, Qinggui, Ma, Yun, Lin, Rui, Yi, Xianlin, Lu, Haoyuan, Bai, Xianzhong, Cheng, Jiwen
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container_title Journal of cellular biochemistry
container_volume 120
creator Ye, Xinqing
Guo, Jinan
Zhang, Hongxiang
Meng, Qinggui
Ma, Yun
Lin, Rui
Yi, Xianlin
Lu, Haoyuan
Bai, Xianzhong
Cheng, Jiwen
description Estrogen‐related receptor α (ERRα) belongs to the superfamily of nuclear orphan receptors. However, the role of ERRα in bladder cancer remains unknown. This study examined the expression of ERRα in bladder cancer tissues and explored the molecular mechanisms of ERRα in bladder cancer progression. The expression of ERRα in bladder cancer tissues from 61 patients was determined by immunohistochemistry. We performed quantitative real‐time polymerase chain reaction assay to detect the gene expression levels and carried out Western blot assay to measure protein levels. In vitro functional assays, including colony formation, Cell Counting Kit‐8, Transwell invasion, and migration assays, were performed to detect bladder cancer cell growth, proliferation, invasion, and migration, respectively. Flow cytometry was used to determine the cell apoptotic rate of bladder cancer cells. Among the 61 detected bladder cancer tissues, 39 bladder cancer tissues showed positive ERRα immunoreactivity. Higher ERRα immunoreactivity score was significantly associated with TNM stage, tumor grade, distant metastasis, and poor survival in patients with bladder cancer. Univariate and multivariate analyses showed that ERRα immunoreactivity was an independent prognostic factor for overall survival in patients with bladder cancer. ERRα was found to be upregulated in bladder cancer cell lines, and knockdown of ERRα suppressed bladder cancer cell growth, proliferation, invasion, and migration; promoted bladder cancer cell apoptosis; and inhibited the epithelial‐mesenchymal transition of bladder cancer cells. On the other hand, bladder cancer cell proliferation, invasion, and migration were significantly enhanced after cells were transfected with an ERRα‐overexpressing vector. In vivo tumor growth and metastasis assays showed that ERRα knockdown resulted in remarkable inhibition of tumor growth and tumor metastasis in nude mice. Collectively, our results suggest that the enhanced expression of ERRα may play a key role in the development and progression of bladder cancer and ERRα may serve as an important prognostic factor for bladder cancer. Estrogen‐related receptor α (ERRα) belongs to a class of nuclear orphan receptors. However, the role of ERRα in bladder cancer remains unknown. The data from the present study suggest that the enhanced expression of ERRα may play a key role in the development and progression of bladder cancer and serve as an important prognostic factor for bladder cancer
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However, the role of ERRα in bladder cancer remains unknown. This study examined the expression of ERRα in bladder cancer tissues and explored the molecular mechanisms of ERRα in bladder cancer progression. The expression of ERRα in bladder cancer tissues from 61 patients was determined by immunohistochemistry. We performed quantitative real‐time polymerase chain reaction assay to detect the gene expression levels and carried out Western blot assay to measure protein levels. In vitro functional assays, including colony formation, Cell Counting Kit‐8, Transwell invasion, and migration assays, were performed to detect bladder cancer cell growth, proliferation, invasion, and migration, respectively. Flow cytometry was used to determine the cell apoptotic rate of bladder cancer cells. Among the 61 detected bladder cancer tissues, 39 bladder cancer tissues showed positive ERRα immunoreactivity. Higher ERRα immunoreactivity score was significantly associated with TNM stage, tumor grade, distant metastasis, and poor survival in patients with bladder cancer. Univariate and multivariate analyses showed that ERRα immunoreactivity was an independent prognostic factor for overall survival in patients with bladder cancer. ERRα was found to be upregulated in bladder cancer cell lines, and knockdown of ERRα suppressed bladder cancer cell growth, proliferation, invasion, and migration; promoted bladder cancer cell apoptosis; and inhibited the epithelial‐mesenchymal transition of bladder cancer cells. On the other hand, bladder cancer cell proliferation, invasion, and migration were significantly enhanced after cells were transfected with an ERRα‐overexpressing vector. In vivo tumor growth and metastasis assays showed that ERRα knockdown resulted in remarkable inhibition of tumor growth and tumor metastasis in nude mice. Collectively, our results suggest that the enhanced expression of ERRα may play a key role in the development and progression of bladder cancer and ERRα may serve as an important prognostic factor for bladder cancer. Estrogen‐related receptor α (ERRα) belongs to a class of nuclear orphan receptors. However, the role of ERRα in bladder cancer remains unknown. The data from the present study suggest that the enhanced expression of ERRα may play a key role in the development and progression of bladder cancer and serve as an important prognostic factor for bladder cancer.</description><identifier>ISSN: 0730-2312</identifier><identifier>EISSN: 1097-4644</identifier><identifier>DOI: 10.1002/jcb.28657</identifier><identifier>PMID: 30977157</identifier><language>eng</language><publisher>United States: Wiley Subscription Services, Inc</publisher><subject>Adult ; Aged ; Animals ; Apoptosis ; Assaying ; Bladder ; Bladder cancer ; Cancer ; Cell growth ; Cell Line, Tumor ; Cell migration ; Cell Movement ; Cell Proliferation ; Epithelial-Mesenchymal Transition ; ERRalpha Estrogen-Related Receptor ; Estrogen Receptor alpha - metabolism ; Estrogens ; estrogen‐related receptor α ; Female ; Flow cytometry ; Gene expression ; Gene Knockdown Techniques ; Health risk assessment ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Male ; Mesenchyme ; Metastases ; Metastasis ; Mice, Nude ; Middle Aged ; Molecular modelling ; Multivariate Analysis ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Orphan receptors ; overall survival ; Polymerase chain reaction ; proliferation ; Receptors ; Receptors, Estrogen - metabolism ; Survival ; Tissues ; Tumor cell lines ; Tumors ; Urinary Bladder Neoplasms - metabolism ; Urinary Bladder Neoplasms - pathology</subject><ispartof>Journal of cellular biochemistry, 2019-08, Vol.120 (8), p.13841-13852</ispartof><rights>2019 Wiley Periodicals, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3537-82665c9bb55416c4905ce5a418ccb8f63ca69956cb2003cd0c30ebefbef077cb3</citedby><cites>FETCH-LOGICAL-c3537-82665c9bb55416c4905ce5a418ccb8f63ca69956cb2003cd0c30ebefbef077cb3</cites><orcidid>0000-0002-5566-2402</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fjcb.28657$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fjcb.28657$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1416,27923,27924,45573,45574</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30977157$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ye, Xinqing</creatorcontrib><creatorcontrib>Guo, Jinan</creatorcontrib><creatorcontrib>Zhang, Hongxiang</creatorcontrib><creatorcontrib>Meng, Qinggui</creatorcontrib><creatorcontrib>Ma, Yun</creatorcontrib><creatorcontrib>Lin, Rui</creatorcontrib><creatorcontrib>Yi, Xianlin</creatorcontrib><creatorcontrib>Lu, Haoyuan</creatorcontrib><creatorcontrib>Bai, Xianzhong</creatorcontrib><creatorcontrib>Cheng, Jiwen</creatorcontrib><title>The enhanced expression of estrogen‐related receptor α in human bladder cancer tissues and the effects of estrogen‐related receptor α knockdown on bladder cancer cells</title><title>Journal of cellular biochemistry</title><addtitle>J Cell Biochem</addtitle><description>Estrogen‐related receptor α (ERRα) belongs to the superfamily of nuclear orphan receptors. However, the role of ERRα in bladder cancer remains unknown. This study examined the expression of ERRα in bladder cancer tissues and explored the molecular mechanisms of ERRα in bladder cancer progression. The expression of ERRα in bladder cancer tissues from 61 patients was determined by immunohistochemistry. We performed quantitative real‐time polymerase chain reaction assay to detect the gene expression levels and carried out Western blot assay to measure protein levels. In vitro functional assays, including colony formation, Cell Counting Kit‐8, Transwell invasion, and migration assays, were performed to detect bladder cancer cell growth, proliferation, invasion, and migration, respectively. Flow cytometry was used to determine the cell apoptotic rate of bladder cancer cells. Among the 61 detected bladder cancer tissues, 39 bladder cancer tissues showed positive ERRα immunoreactivity. Higher ERRα immunoreactivity score was significantly associated with TNM stage, tumor grade, distant metastasis, and poor survival in patients with bladder cancer. Univariate and multivariate analyses showed that ERRα immunoreactivity was an independent prognostic factor for overall survival in patients with bladder cancer. ERRα was found to be upregulated in bladder cancer cell lines, and knockdown of ERRα suppressed bladder cancer cell growth, proliferation, invasion, and migration; promoted bladder cancer cell apoptosis; and inhibited the epithelial‐mesenchymal transition of bladder cancer cells. On the other hand, bladder cancer cell proliferation, invasion, and migration were significantly enhanced after cells were transfected with an ERRα‐overexpressing vector. In vivo tumor growth and metastasis assays showed that ERRα knockdown resulted in remarkable inhibition of tumor growth and tumor metastasis in nude mice. Collectively, our results suggest that the enhanced expression of ERRα may play a key role in the development and progression of bladder cancer and ERRα may serve as an important prognostic factor for bladder cancer. Estrogen‐related receptor α (ERRα) belongs to a class of nuclear orphan receptors. However, the role of ERRα in bladder cancer remains unknown. 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However, the role of ERRα in bladder cancer remains unknown. This study examined the expression of ERRα in bladder cancer tissues and explored the molecular mechanisms of ERRα in bladder cancer progression. The expression of ERRα in bladder cancer tissues from 61 patients was determined by immunohistochemistry. We performed quantitative real‐time polymerase chain reaction assay to detect the gene expression levels and carried out Western blot assay to measure protein levels. In vitro functional assays, including colony formation, Cell Counting Kit‐8, Transwell invasion, and migration assays, were performed to detect bladder cancer cell growth, proliferation, invasion, and migration, respectively. Flow cytometry was used to determine the cell apoptotic rate of bladder cancer cells. Among the 61 detected bladder cancer tissues, 39 bladder cancer tissues showed positive ERRα immunoreactivity. Higher ERRα immunoreactivity score was significantly associated with TNM stage, tumor grade, distant metastasis, and poor survival in patients with bladder cancer. Univariate and multivariate analyses showed that ERRα immunoreactivity was an independent prognostic factor for overall survival in patients with bladder cancer. ERRα was found to be upregulated in bladder cancer cell lines, and knockdown of ERRα suppressed bladder cancer cell growth, proliferation, invasion, and migration; promoted bladder cancer cell apoptosis; and inhibited the epithelial‐mesenchymal transition of bladder cancer cells. On the other hand, bladder cancer cell proliferation, invasion, and migration were significantly enhanced after cells were transfected with an ERRα‐overexpressing vector. In vivo tumor growth and metastasis assays showed that ERRα knockdown resulted in remarkable inhibition of tumor growth and tumor metastasis in nude mice. Collectively, our results suggest that the enhanced expression of ERRα may play a key role in the development and progression of bladder cancer and ERRα may serve as an important prognostic factor for bladder cancer. Estrogen‐related receptor α (ERRα) belongs to a class of nuclear orphan receptors. However, the role of ERRα in bladder cancer remains unknown. The data from the present study suggest that the enhanced expression of ERRα may play a key role in the development and progression of bladder cancer and serve as an important prognostic factor for bladder cancer.</abstract><cop>United States</cop><pub>Wiley Subscription Services, Inc</pub><pmid>30977157</pmid><doi>10.1002/jcb.28657</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0002-5566-2402</orcidid></addata></record>
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subjects Adult
Aged
Animals
Apoptosis
Assaying
Bladder
Bladder cancer
Cancer
Cell growth
Cell Line, Tumor
Cell migration
Cell Movement
Cell Proliferation
Epithelial-Mesenchymal Transition
ERRalpha Estrogen-Related Receptor
Estrogen Receptor alpha - metabolism
Estrogens
estrogen‐related receptor α
Female
Flow cytometry
Gene expression
Gene Knockdown Techniques
Health risk assessment
Humans
Immunohistochemistry
Kaplan-Meier Estimate
Male
Mesenchyme
Metastases
Metastasis
Mice, Nude
Middle Aged
Molecular modelling
Multivariate Analysis
Neoplasm Invasiveness
Neoplasm Metastasis
Orphan receptors
overall survival
Polymerase chain reaction
proliferation
Receptors
Receptors, Estrogen - metabolism
Survival
Tissues
Tumor cell lines
Tumors
Urinary Bladder Neoplasms - metabolism
Urinary Bladder Neoplasms - pathology
title The enhanced expression of estrogen‐related receptor α in human bladder cancer tissues and the effects of estrogen‐related receptor α knockdown on bladder cancer cells
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