Transcriptome-wide identification of key regulatory networks in drug resistant cancer cells

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K21634
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Tumor therapeutics; System genome science
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: HUANG Yi 国立研究開発法人理化学研究所, ライフサイエンス技術基盤研究センター, 特別研究員 (60750289)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: Cancer / Drug / CAGE / FANTOM / Adverse Effects / Drug Repositioning / Statin

Outline of Final Research Achievements

In order to identify alternative or combinatorial therapeutic strategies to overcome drug resistance of cancer cells, we firstly developed an analytic framework that can dissect the effects of drugs, which could be adverse effects or new usages. We selected Statins as an example to evaluate our framework. Several studies have suggested that Statins may have potential as cancer therapy in human malignancies. In contrast, some studies revealed that Statins increase cancer risk of prostate cancer. However, the detail of mechanisms of these unexpected effects are still not clear. Applying our framework to treatment of three different cell types with four widely used Statins, we identified significantly associated pairs of transcriptional factors and pathways, and infer regulatory networks to elucidate the regulation of on/off target pathways. We show that our framework provides new insights about the drug effects under study, and helps identification of new usages or potential side effects

Free Research Field

Systems Biology