Metabolic changes in bladder cancer

Woolbright, Benjamin L.; Ayres, Matthew P.; Taylor, John A.

doi:10.1016/j.urolonc.2018.04.010

Cited by 41 publications

(38 citation statements)

References 121 publications

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“…52 Future prospective validation using larger cohorts is necessary to confirm these findings, and a further functional investigation is needed to establish the roles of ME3, KDM2A, and P3H2 in BLCA disparities. We have found that high levels of circulating hypoxanthine, uric acid, taurine, and the amino acids glutamine, serine, asparagine, valine, glycine, and lysine have the potential to discriminate between AA and EA patients with BLCA.…”

Section: Discussionmentioning

confidence: 97%

“…These changes could potentially be targeted for therapeutic applications. 52 Future prospective validation using larger cohorts is necessary to confirm these findings, and a further functional investigation is needed to establish the roles of ME3, KDM2A, and P3H2 in BLCA disparities. Finally, this study highlights many unique metabolites and metabolic pathways that can lead to the identification of new biochemical nodes that contribute to racial disparities in BLCA development.…”

Section: Discussionmentioning

confidence: 97%

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Large‐scale profiling of serum metabolites in African American and European American patients with bladder cancer reveals metabolic pathways associated with patient survival

Vantaku

Donepudi

Piyarathna

et al. 2019

Cancer

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BACKGROUND: African Americans (AAs) experience a disproportionally high rate of bladder cancer (BLCA) deaths even though their incidence rates are lower than those of other patient groups. Using a metabolomics approach, this study investigated how AA BLCA may differ molecularly from European Americans (EAs) BLCA, and it examined serum samples from patients with BLCA with the aim of identifying druggable metabolic pathways in AA patients. METHODS: Targeted metabolomics was applied to measure more than 300 metabolites in serum samples from 2 independent cohorts of EA and AA patients with BLCA and healthy EA and AA controls via liquid chromatography-mass spectrometry, and this was followed by the identification of altered metabolic pathways with a focus on AA BLCA. A subset of the differential metabolites was validated via absolute quantification with the Biocrates AbsoluteIDQ p180 kit. The clinical significance of the findings was further examined in The Cancer Genomic Atlas BLCA data set. RESULTS: Fifty-three metabolites, mainly related to amino acid, lipid, and nucleotide metabolism, were identified that showed significant differences in abundance between AA and EA BLCA. For example, the levels of taurine, glutamine, glutamate, aspartate, and serine were elevated in serum samples from AA patients versus EA patients. By mapping these metabolites to genes, this study identified significant relations with regulators of metabolism such as malic enzyme 3, prolyl 3-hydroxylase 2, and lysine demethylase 2A that predicted patient survival exclusively in AA patients with BLCA. CONCLUSIONS: This metabolic profile of serum samples might be used to assess risk progression in AA BLCA. These first-in-field findings describe metabolic alterations in AA BLCA and emphasize a potential biological basis for BLCA health disparities. Cancer 2019;125:921-932.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 97%

Large‐scale profiling of serum metabolites in African American and European American patients with bladder cancer reveals metabolic pathways associated with patient survival

Vantaku

Donepudi

Piyarathna

et al. 2019

Cancer

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“…4 Multistep processes, including the accumulation of several structural and genomic alterations and variations in cellular metabolism and intracellular signaling pathways, has been speculated to be reasons for bladder oncogenesis. 5 Radical surgery and radiotherapy are current standard therapeutic methods of BC. However, despite undergoing systemic therapies, almost one-quarter of MIBC patients face an unfavorable prognosis.…”

Section: Introductionmentioning

confidence: 99%

The role of exosomal miR‐375‐3p: A potential suppressor in bladder cancer via the Wnt/β‐catenin pathway

Huyan

Cai

et al. 2020

FASEB j.

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miR‐375‐3p is a significantly downregulated miRNA in bladder cancer (BC). However, its role in BC regulation is still unclear. In this study, we reported that miR‐375‐3p overexpression inhibited proliferation and migration and promoted apoptosis in BC cells. Frizzled‐8 (FZD8) gene is identified as the direct miR‐375‐3p targeting gene. miR‐375‐3p blocks the Wnt/β‐catenin pathway and downstream molecules Cyclin D1 and c‐Myc by inhibiting the expression of FZD8 directly, it could increase caspase 1 and caspase 3 expression and promote T24 cell apoptosis as well. miR‐375‐3p also showed a significant inhibitory effect in vivo in bladder tumor‐bearing nude mice, as demonstrated by the reduced tumor volume and Ki67 proliferation index in tumor tissue. Collectively, miR‐375‐3p is a suppressor of BC that inhibits proliferation and metastasis, and promotes apoptosis in BC cells as well as suppresses tumor growth in a T24 xenograft mouse model, which could be used as a potential therapeutic approach for BC in future.

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“…Despite great progress has been made in individualized and systemic treatments of bladder cancer in the past years, the incidence and modality of the disease remains increasing . Bladder cancer is the result of a multistep process which involves the accumulation of several structural and genomic alterations, gene expression profile, and intracellular signal pathway alterations . Therefore, better understanding of the underlying mechanisms responsible for bladder cancer progression may facilitate the identification of novel therapeutic targets for the treatment of bladder cancer.…”

Section: Introductionmentioning

confidence: 99%

“…CHEN Et al. and intracellular signal pathway alterations. 3 Therefore, better understanding of the underlying mechanisms responsible for bladder cancer progression may facilitate the identification of novel therapeutic targets for the treatment of bladder cancer.…”

mentioning

confidence: 99%

miR‐190b promotes tumor growth and metastasis via suppressing NLRC3 in bladder carcinoma

et al. 2020

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Bladder cancer is one of the most common urogenital malignancies. However, its pathogenesis, especially molecular mechanisms remain elusive. Thus, understanding the molecular mechanisms underlying bladder cancer is important for the discovery of novel therapeutic paradigms for these diseases. In current study, we found that micro‐RNA (miR)‐190b is highly expressed in bladder cancer tissues and cells. Overexpression of miR‐190b enhanced the proliferation, growth, migration and invasion capabilities, and angiogenesis of bladder cancer cells, whereas downregulation of miR‐190b reversed these effects. Target prediction and dual luciferase reporter assays identified NLR family CARD domain containing 3 (NLRC3) as a potential target of miR‐190b. Pathway analysis indicated that miR‐190b promotes bladder cancer progression via the Wnt/β‐catenin and mTOR signaling pathways. Taken together, our findings imply that miR‐190b acts as a critical regulator for bladder cancer development by repressing NLRC3 and partly through the Wnt/β‐catenin and mTOR pathways. Our study suggests that miR‐190b may be served as a potential therapeutic target for bladder cancer treatment.

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Metabolic changes in bladder cancer

Cited by 41 publications

References 121 publications

Large‐scale profiling of serum metabolites in African American and European American patients with bladder cancer reveals metabolic pathways associated with patient survival

Large‐scale profiling of serum metabolites in African American and European American patients with bladder cancer reveals metabolic pathways associated with patient survival

The role of exosomal miR‐375‐3p: A potential suppressor in bladder cancer via the Wnt/β‐catenin pathway

miR‐190b promotes tumor growth and metastasis via suppressing NLRC3 in bladder carcinoma

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