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ArticleInternational urology and nephrology2025

Overexpression of BMAL-1 is related to progression of urothelial carcinoma in arsenic exposure area.

Yu-Jui Wu, Shu-Jyuan Chang, Yen-Shuo Huang, Chee-Yin Chai

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Article in International urology and nephrology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

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1citing papers in PubMed
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1 citing paper in PubMed.

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5 · Who and what money

Authors and funding

4 authors.

Yu-Jui Wu *School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Shu-Jyuan Chang *Department of Pathology, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Yen-Shuo HuangDepartment of Pathology, Kaohsiung Medical University Hospital, No.100, Tzyou 1St Road, Kaohsiung, 807, Taiwan.
Chee-Yin ChaiDepartment of Pathology, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. cychai@kmu.edu.tw.

Funding

National Science and Technology Council, Taiwan. NSTC 112-2813-C-037-031-B
6 · The paper itself

Abstract

backgroundEnvironmental exposure to arsenic has long been associated with various clinical and pathophysiological aspects of urothelial carcinoma (UC), although the role of arsenic in UC and its impact on circadian proteins, particularly BMAL-1, remains unestablished. Previous research suggests that arsenic upregulates Aurora kinase A (AURKA), subsequently inhibiting GSK-3β, which might lead to overexpression of BMAL-1; nevertheless, the underlying pathway and its clinical significance in UC with arsenic exposure have yet to be validated. This study focuses on two potential upstream regulators of BMAL-1, AURKA and GSK-3β.

methodsNinety-nine tumor tissue samples were retrospectively collected along with their respective clinical data. Immunohistochemistry was employed to assess the expression of each protein.

resultsA positive relationship was observed between the expression levels of AURKA and BMAL-1 (p < 0.001), while negative correlations were noted between the expression levels of GSK-3β and AURKA (p < 0.001), and between GSK-3β and BMAL-1 (p = 0.003). Tissue samples exposed to arsenic exhibited significantly higher levels of AURKA (p < 0.001) and BMAL-1 (p < 0.001), a markedly lower expression of GSK-3β (p = 0.001), alongside a decreased survival status (p = 0.025) compared to non-exposed samples. Furthermore, patients with UC of higher tumor grade tended to show increased levels of AURKA (p < 0.001), BMAL-1 (p < 0.001), and decreased levels of GSK-3β (p < 0.001). Elevated expression of AURKA (p < 0.001) and BMAL-1 (p = 0.002), as well as reduced expression of GSK-3β (p = 0.003), were also associated with a decreased survival status.

conclusionsThis study highlights the differential expression of BMAL-1, AURKA, and GSK-3β in association with arsenic exposure and their significant impact on clinical and pathological features of UC. Moreover, BMAL-1, AURKA, and GSK-3β emerge as potential prognostic markers for UC in regions with arsenic exposure.

Indexed as

ARNTL Transcription FactorsArsenicAurora Kinase ACarcinoma, Transitional CellEnvironmental ExposureGlycogen Synthase Kinase 3 betaUrinary Bladder NeoplasmsAdultAgedDisease ProgressionFemaleHumansMaleMiddle AgedRetrospective StudiesARNTL Transcription FactorsArsenicAURKA protein, humanAurora Kinase ABMAL1 protein, humanGlycogen Synthase Kinase 3 betaArsenicAurora kinase ABMAL-1GSK-3βUrothelial Carcinoma

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.