Elucidation of regulatory interaction networks underlying human prostate adenocarcinoma

doi:10.5246/jcps.2015.01.002

中国药学(英文版) ›› 2015, Vol. 24 ›› Issue (1): 12-27.DOI: 10.5246/jcps.2015.01.002

Elucidation of regulatory interaction networks underlying human prostate adenocarcinoma

Sujit Nair^1,2, Celine Liew³, Tin-Oo Khor², Li Cai⁴, Ah-Ng Tony Kong^2*

1. Amrita Cancer Discovery Biology Laboratory and Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham University, Ponekkara P.O., Kochi-682041, Kerala, India
2. Department of Pharmaceutics, Rutgers, The State University of New Jersey, Piscataway, NJ-08854, USA
3. Department of Pharmacy, National University of Singapore, 18, Science Drive 4, Singapore-117543
4. Department of Biomedical Engineering, Rutgers, the State University of New Jersey, Piscataway, NJ-08854, USA

收稿日期:2014-09-26 修回日期:2014-11-14 出版日期:2015-01-15 发布日期:2014-11-15
通讯作者: Tel.: +848-445-6369/8, Fax: +732-445-3134
基金资助:
RO1 CA 094828 to Prof. Ah-Ng Tony Kong and in part by R21 CA133675 to Dr. Li Cai both from the National Institutes of Health (NIH).

Elucidation of regulatory interaction networks underlying human prostate adenocarcinoma

Sujit Nair^1,2, Celine Liew³, Tin-Oo Khor², Li Cai⁴, Ah-Ng Tony Kong^2*

1. Amrita Cancer Discovery Biology Laboratory and Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham University, Ponekkara P.O., Kochi-682041, Kerala, India
2. Department of Pharmaceutics, Rutgers, The State University of New Jersey, Piscataway, NJ-08854, USA
3. Department of Pharmacy, National University of Singapore, 18, Science Drive 4, Singapore-117543
4. Department of Biomedical Engineering, Rutgers, the State University of New Jersey, Piscataway, NJ-08854, USA

Received:2014-09-26 Revised:2014-11-14 Online:2015-01-15 Published:2014-11-15
Contact: Tel.: +848-445-6369/8, Fax: +732-445-3134
Supported by:
RO1 CA 094828 to Prof. Ah-Ng Tony Kong and in part by R21 CA133675 to Dr. Li Cai both from the National Institutes of Health (NIH).

摘要/Abstract

摘要：

The incidence of prostate cancer is rising in the Asia-Pacific region as well as other countries. Androgen-ablation therapy is clinically useful in the androgen-dependent phenotype; however, many patients progress to hormone refractory prostate cancer that is difficult to treat and needs newer interventions that are more effective. The objective of this study was to determine functionally-relevant biological networks, to appreciate the potential crosstalk between signaling members, and to identify biomarker signatures in prostate cancer. We used microarray analyses to identify key genes that were upregulated or down regulated at least five-fold in human prostate cancer and constructed canonical interaction networks that are important in prostate cancer through metabolomics analyses. Our prostate cancer network architecture revealed several key biomarkers including ERK1/2, JNK, p38, MEK, PI3K, NFκB, AP-1, 14-3-3, VEGF, PDGF, Rb, WNT8A, WNT10A, CD44, ESR2, FSH and LH. Furthermore, the top ten transcription factors identified by TFBS-association signature analysis in the regulatory elements of co-regulated biomarkers were delineated, which may crosstalk with upstream or downstream genes elicited in our network architecture. Taken together, our results demonstrate that the regulatory interaction networks in prostate cancer provide a universal view of crosstalk between important biomarkers, i.e., key players in the pathogenesis of this disease. This will facilitate more rapid screening of functional biomarkers in early/intermediate drug discovery.

关键词: Human prostate cancer, Microarray, Biological network, Biomarker

Abstract:

Key words: Human prostate cancer, Microarray, Biological network, Biomarker

中图分类号:

R962

Supporting:

Sujit Nair, Celine Liew, Tin-Oo Khor, Li Cai, Ah-Ng Tony Kong. Elucidation of regulatory interaction networks underlying human prostate adenocarcinoma[J]. 中国药学(英文版), 2015, 24(1): 12-27.

Sujit Nair, Celine Liew, Tin-Oo Khor, Li Cai, Ah-Ng Tony Kong. Elucidation of regulatory interaction networks underlying human prostate adenocarcinoma[J]. Journal of Chinese Pharmaceutical Sciences, 2015, 24(1): 12-27.

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Elucidation of regulatory interaction networks underlying human prostate adenocarcinoma

Elucidation of regulatory interaction networks underlying human prostate adenocarcinoma

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