BUB1 drives the occurrence and development of bladder cancer by mediating the STAT3 signaling pathway

Abstract Background The incidence of bladder urothelial carcinoma (UC), a common malignancy of the urinary tract, is approximately three times higher in men than in women. High expression of the mitotic kinase BUB1 is associated with the occurrence and development of several cancers, although the re...

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Autores principales:	Ning Jiang, Yihao Liao, Miaomiao Wang, Youzhi Wang, Keke Wang, Jianing Guo, Peikang Wu, Boqiang Zhong, Tao Guo, Changli Wu
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Bladder cancer BUB1 STAT3 Phosphorylation Proliferation Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/925d1e6364bd4201b0db1f6a544595eb
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spelling	oai:doaj.org-article:925d1e6364bd4201b0db1f6a544595eb2021-12-05T12:10:09ZBUB1 drives the occurrence and development of bladder cancer by mediating the STAT3 signaling pathway10.1186/s13046-021-02179-z1756-9966https://doaj.org/article/925d1e6364bd4201b0db1f6a544595eb2021-12-01T00:00:00Zhttps://doi.org/10.1186/s13046-021-02179-zhttps://doaj.org/toc/1756-9966Abstract Background The incidence of bladder urothelial carcinoma (UC), a common malignancy of the urinary tract, is approximately three times higher in men than in women. High expression of the mitotic kinase BUB1 is associated with the occurrence and development of several cancers, although the relationship between BUB1 and bladder tumorigenesis remains unclear. Methods Using a microarray approach, we found increased BUB1 expression in human BCa. The association between BUB1 and STAT3 phosphorylation was determined through molecular and cell biological methods. We evaluated the impact of pharmacologic inhibition of BUB1 kinase activity on proliferation and BCa progression in vitro and in vivo. Results In this study, we found that BUB1 expression was increased in human bladder cancer (BCa). We further identified through a series of molecular and cell biological approaches that BUB1 interacted directly with STAT3 and mediated the phosphorylation of STAT3 at Ser727. In addition, the findings that pharmacologic inhibition of BUB1 kinase activity significantly suppressed BCa cell proliferation and the progression of bladder cancer in vitro and in vivo were further verified. Finally, we found that the BUB1/STAT3 complex promoted the transcription of STAT3 target genes and that depletion of BUB1 and mutation of the BUB1 kinase domain abrogated this transcriptional activity, further highlighting the critical role of kinase activity in the activation of STAT3 target genes. A pharmacological inhibitor of BUB1 (2OH-BNPP1) was able to significantly inhibit the growth of BCa cell xenografts. Conclusion This study showed that the BUB1 kinase drives the progression and proliferation of BCa by regulating the transcriptional activation of STAT3 signaling and may be an attractive candidate for therapeutic targeting in BCa.Ning JiangYihao LiaoMiaomiao WangYouzhi WangKeke WangJianing GuoPeikang WuBoqiang ZhongTao GuoChangli WuBMCarticleBladder cancerBUB1STAT3PhosphorylationProliferationNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENJournal of Experimental & Clinical Cancer Research, Vol 40, Iss 1, Pp 1-17 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Bladder cancer BUB1 STAT3 Phosphorylation Proliferation Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Bladder cancer BUB1 STAT3 Phosphorylation Proliferation Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Ning Jiang Yihao Liao Miaomiao Wang Youzhi Wang Keke Wang Jianing Guo Peikang Wu Boqiang Zhong Tao Guo Changli Wu BUB1 drives the occurrence and development of bladder cancer by mediating the STAT3 signaling pathway
description	Abstract Background The incidence of bladder urothelial carcinoma (UC), a common malignancy of the urinary tract, is approximately three times higher in men than in women. High expression of the mitotic kinase BUB1 is associated with the occurrence and development of several cancers, although the relationship between BUB1 and bladder tumorigenesis remains unclear. Methods Using a microarray approach, we found increased BUB1 expression in human BCa. The association between BUB1 and STAT3 phosphorylation was determined through molecular and cell biological methods. We evaluated the impact of pharmacologic inhibition of BUB1 kinase activity on proliferation and BCa progression in vitro and in vivo. Results In this study, we found that BUB1 expression was increased in human bladder cancer (BCa). We further identified through a series of molecular and cell biological approaches that BUB1 interacted directly with STAT3 and mediated the phosphorylation of STAT3 at Ser727. In addition, the findings that pharmacologic inhibition of BUB1 kinase activity significantly suppressed BCa cell proliferation and the progression of bladder cancer in vitro and in vivo were further verified. Finally, we found that the BUB1/STAT3 complex promoted the transcription of STAT3 target genes and that depletion of BUB1 and mutation of the BUB1 kinase domain abrogated this transcriptional activity, further highlighting the critical role of kinase activity in the activation of STAT3 target genes. A pharmacological inhibitor of BUB1 (2OH-BNPP1) was able to significantly inhibit the growth of BCa cell xenografts. Conclusion This study showed that the BUB1 kinase drives the progression and proliferation of BCa by regulating the transcriptional activation of STAT3 signaling and may be an attractive candidate for therapeutic targeting in BCa.
format	article
author	Ning Jiang Yihao Liao Miaomiao Wang Youzhi Wang Keke Wang Jianing Guo Peikang Wu Boqiang Zhong Tao Guo Changli Wu
author_facet	Ning Jiang Yihao Liao Miaomiao Wang Youzhi Wang Keke Wang Jianing Guo Peikang Wu Boqiang Zhong Tao Guo Changli Wu
author_sort	Ning Jiang
title	BUB1 drives the occurrence and development of bladder cancer by mediating the STAT3 signaling pathway
title_short	BUB1 drives the occurrence and development of bladder cancer by mediating the STAT3 signaling pathway
title_full	BUB1 drives the occurrence and development of bladder cancer by mediating the STAT3 signaling pathway
title_fullStr	BUB1 drives the occurrence and development of bladder cancer by mediating the STAT3 signaling pathway
title_full_unstemmed	BUB1 drives the occurrence and development of bladder cancer by mediating the STAT3 signaling pathway
title_sort	bub1 drives the occurrence and development of bladder cancer by mediating the stat3 signaling pathway
publisher	BMC
publishDate	2021
url	https://doaj.org/article/925d1e6364bd4201b0db1f6a544595eb
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_version_	1718372205606207488

BUB1 drives the occurrence and development of bladder cancer by mediating the STAT3 signaling pathway

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