Transcription factor and microRNA regulation in androgen-dependent and -independent prostate cancer cells

Guohua Wang, Yadong Wang, Weixing Feng, Xin Wang, Jack Y. Yang, Yuming Zhao, Yue Wang, Yunlong Liu

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

Background: Prostate cancer is one of the leading causes of cancer death in men. Androgen ablation, the most commonly-used therapy for progressive prostate cancer, is ineffective once the cancer cells become androgen-independent. The regulatory mechanisms that cause this transition (from androgen-dependent to androgen-independent) remain unknown. In this study, based on the microarray data comparing global gene expression patterns in the prostate tissue between androgen-dependent and -independent prostate cancer patients, we indentify a set of transcription factors and microRNAs that potentially cause such difference, using a model-based computational approach. Results: From 335 position weight matrices in the TRANSFAC database and 564 microRNAs in the microRNA registry, our model identify 5 transcription factors and 7 microRNAs to be potentially responsible for the level of androgen dependency. Of these transcription factors and microRNAs, the estimated function of all the 5 transcription factors are predicted to be inhibiting transcription in androgen-independent samples comparing with the dependent ones. Six out of 7 microRNAs, however, demonstrated stimulatory effects. We also find that the expression levels of three predicted transcription factors, including AP-1, STAT3 (signal transducers and activators of transcription 3), and DBP (albumin D-box) are significantly different between androgen-dependent and -independent patients. In addition, microRNA microarray data from other studies confirm that several predicted microRNAs, including miR-21, miR-135a, and miR-135b, demonstrate differential expression in prostate cancer cells, comparing with normal tissues. Conclusion: We present a model-based computational approach to identify transcription factors and microRNAs influencing the progression of androgen-dependent prostate cancer to androgen-independent prostate cancer. This result suggests that the capability of transcription factors to initiate transcription and microRNAs to facilitate mRNA degradation are both decreased in androgen-independent prostate cancer. The proposed model-based approach indicates that considering combinatorial effects of transcription factors and microRNAs in a unified model provides additional transcriptional and post-transcriptional regulatory mechanisms on global gene expression in the prostate cancer with different hormone-dependency.

Original languageEnglish
Article numberS22
JournalBMC Genomics
Volume9
Issue numberSUPPL. 2
DOIs
StatePublished - Sep 16 2008

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MicroRNAs
Androgens
Prostatic Neoplasms
Transcription Factors
T Cell Transcription Factor 1
Position-Specific Scoring Matrices
Gene Expression
STAT3 Transcription Factor
Transcription Factor AP-1
RNA Stability
Registries
Prostate
Cause of Death
Albumins
Neoplasms
Databases
Hormones

ASJC Scopus subject areas

  • Biotechnology
  • Genetics

Cite this

Transcription factor and microRNA regulation in androgen-dependent and -independent prostate cancer cells. / Wang, Guohua; Wang, Yadong; Feng, Weixing; Wang, Xin; Yang, Jack Y.; Zhao, Yuming; Wang, Yue; Liu, Yunlong.

In: BMC Genomics, Vol. 9, No. SUPPL. 2, S22, 16.09.2008.

Research output: Contribution to journalArticle

Wang, Guohua ; Wang, Yadong ; Feng, Weixing ; Wang, Xin ; Yang, Jack Y. ; Zhao, Yuming ; Wang, Yue ; Liu, Yunlong. / Transcription factor and microRNA regulation in androgen-dependent and -independent prostate cancer cells. In: BMC Genomics. 2008 ; Vol. 9, No. SUPPL. 2.
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