The emerging role of the androgen receptor in bladder cancer

Lombard, Alan P.; Mudryj, Maria

doi:10.1530/erc-15-0209

Cited by 54 publications

(50 citation statements)

References 94 publications

(130 reference statements)

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“…A variety of experimentally validated target genes regulated by hsa-miR-31-5p has been described in different tumor types [26], including AR and DNMT3A genes. The androgen receptor (AR) is a critical transcription factor with prognostic value in breast cancer and prostate [28, 29] as well as in bladder carcinomas [30]. …”

Section: Discussionmentioning

confidence: 99%

Integrative miRNA and mRNA analysis in penile carcinomas reveals markers and pathways with potential clinical impact

et al. 2017

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Penile carcinoma (PeCa) is an important public health issue in poor and developing countries, and has only recently been explored in terms of genetic and epigenetic studies. Integrative data analysis is a powerful method for the identification of molecular drivers involved in cancer development and progression. miRNA and mRNA expression profiles followed by integrative analysis were investigated in 23 PeCa and 12 non-neoplastic penile tissues (NPT). Expression levels of eight miRNAs and 10 mRNAs were evaluated in the same set of samples used for microarray and in a validation set of cases (PeCa = 36; NPT = 27). Eighty-one miRNAs and 2,697 mRNAs were identified as differentially expressed in PeCa. Integrative data analysis revealed 255 mRNAs potentially regulated by 68 miRNAs. Using RT-qPCR, eight miRNAs and nine transcripts were confirmed as altered in PeCa. We identified that MMP1, MMP12 and PPARG and hsa-miR-31-5p, hsa-miR-224-5p, and hsa-miR-223-3p were able to distinguish tumors from NPT with high sensitivity and specificity. Higher MMP1 expression was detected as a better predictor of lymph node metastasis than the clinical-pathological data. In addition, PPARG and EGFR were highlighted as potential pathways for targeted therapy in PeCa. The analysis based on HPV positivity (7 of 23 cases) revealed five miRNA and 13 mRNA differentially expressed. Although in a limited number of cases, HPV positive PeCa presented less aggressive phenotype in comparison with negative cases. Overall, an integrative analysis using mRNA and miRNA profiles revealed markers related with tumor development and progression. Furthermore, MMP1 expression level was a predictive marker for lymph node metastasis in patients with PeCa.

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Section: Discussionmentioning

confidence: 99%

Integrative miRNA and mRNA analysis in penile carcinomas reveals markers and pathways with potential clinical impact

et al. 2017

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“…As a transcription factor, it mediates physiological activities by binding to androgen. It has been demonstrated that androgen signaling has been linked to regulation of proliferation, motility and cell death in urinary malignancies (28,29). Importantly, it has essential roles in malignancies of the prostate, bladder, kidney, lung, breast and liver (30)(31)(32).…”

Section: Discussionmentioning

confidence: 99%

Expression and clinical significance of androgen receptor in bladder cancer: A meta-analysis

Chen

Liu

et al. 2017

Molecular and Clinical Oncology

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Abstract. Emerging evidence has demonstrated that androgen receptor (AR) is a promising therapeutic target for bladder cancer. However, the relationship between AR expression and its clinical significance remains controversial. The present in-depth meta-analysis aimed to investigate the correlation between AR expression and clinicopathological features, as well as prognostic value in bladder cancer. A systematic search was performed from PubMed, Web of Knowledge, Embase and the Cochrane Central Search Library by January 2017. The correlation between AR expression and tumor stage, tumor grade, recurrence free survival and progression free survival for patients with bladder cancer was evaluated. A total of 12 relevant studies with 1,652 patient samples were included. AR expression positively correlated with low tumor grade [odds ratio (OR), 1.95; 95% confidence interval (CI), 1.36-2.81], low tumor stage (OR, 2.06; 95% CI, 1.02-4.16) and low recurrence rate [hazard ratio (HR), 0.48; 95% CI, 0.31-0.75] in Caucasian patients. While, its expression had no significant impact on cancer susceptibility (OR, 1.62; 95% CI, P= 0.44) and progression-free survival (HR, 1.20; 95% CI, P=0.77). The present meta-analysis indicated that AR expression correlates with tumor grade, clinical stage and recurrence rates in the specified population and classification system.Further studies are required to determine the precise role of AR in bladder cancer.

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“…It has been confirmed that AR plays a crucial role in malignancies of the prostate, kidney, breast and bladder cancers [17]. In bladder cancer, high expression of AR has been observed and positively correlated with disease progression [18].…”

Section: Introductionmentioning

confidence: 99%

“…In bladder cancer, high expression of AR has been observed and positively correlated with disease progression [18]. Moreover, AR signaling may also contribute to invasion and metastasis of bladder cancer [17]. …”

Section: Introductionmentioning

confidence: 99%

The Long Non-Coding RNA XIST Interacted with MiR-124 to Modulate Bladder Cancer Growth, Invasion and Migration by Targeting Androgen Receptor (AR)

Xiong

Wang

et al. 2017

Cell Physiol Biochem

101

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Backgrounds/Aims: Long non-coding RNA (lncRNA) X-inactive specific transcript (XIST) is involved in the progression of several tumors. The interaction between lncRNA and miRNA or miRNA’s target genes is reported to play crucial roles in malignancy. In addition, Androgen receptor (AR) is considered to be involved in bladder cancer progression. In this study, we investigated the role of XIST in human bladder cancer and its interaction with miR-124 and AR. Methods: XIST and AR expression was detected in bladder tumor samples and cell lines. Effects of XIST and AR on bladder cancer cells growth, invasion and migration were analyzed. Bioinformatic analysis and luciferase assays were used to identify the interaction among XIST, AR and miR-124. The correlations of miR-124 with XIST and AR in bladder cancer samples were statistically analyzed. Results: XIST and AR were upregulated in bladder cancer tissues and positively correlated. Higher XIST and AR expression were related to poorer TNM stage of bladder cancer. XIST knockdown reduced bladder cancer cells’ proliferation, invasion and migration. While this inhibitory effect could be partially restored by AR overexpression. XIST inhibited miR-124 expression by directly targeting. Moreover, miR-124 could bind to the 3’UTR of AR to regulate its expression. MiR-124 inhibition partially restored the XIST knockdown-induced reduction of AR, c-myc, p27, MMP13 and MMP9 expression. In bladder cancer tissues, miR-124 level was inversely correlated with the expression of XIST and AR, respectively. Conclusion: These findings indicated that XIST might be an oncogenic lncRNA that promoted the bladder cancer growth, invasion and migration via miR-124 dependent AR regulation.

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The emerging role of the androgen receptor in bladder cancer

Cited by 54 publications

References 94 publications

Integrative miRNA and mRNA analysis in penile carcinomas reveals markers and pathways with potential clinical impact

Integrative miRNA and mRNA analysis in penile carcinomas reveals markers and pathways with potential clinical impact

Expression and clinical significance of androgen receptor in bladder cancer: A meta-analysis

The Long Non-Coding RNA XIST Interacted with MiR-124 to Modulate Bladder Cancer Growth, Invasion and Migration by Targeting Androgen Receptor (AR)

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