Biomol Ther.
2017 Sep;25(5):482-489. 10.4062/biomolther.2017.122.
Regulation of Pharmacogene Expression by microRNA in The Cancer Genome Atlas (TCGA) Research Network
- Affiliations
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- 1College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 08826, Republic of Korea. iwkim@snu.ac.kr, jmoh@snu.ac.kr
- 2Office of Clinical Pharmacology, Office of Translational Sciences, Food and Drug Administration, Silver Spring, Maryland 20993, USA.
- 3College of Pharmacy, Gacheon University, Incheon 13120, Republic of Korea.
- KMID: 2389379
- DOI: http://doi.org/10.4062/biomolther.2017.122
Abstract
- Individual differences in drug responses are associated with genetic and epigenetic variability of pharmacogene expression. We aimed to identify the relevant miRNAs which regulate pharmacogenes associated with drug responses. The miRNA and mRNA expression profiles derived from data for normal and solid tumor tissues in The Cancer Genome Atlas (TCGA) Research Network. Predicted miRNAs targeted to pharmacogenes were identified using publicly available databases. A total of 95 pharmacogenes were selected from cholangiocarcinoma and colon adenocarcinoma, as well as kidney renal clear cell, liver hepatocellular, and lung squamous cell carcinomas. Through the integration analyses of miRNA and mRNA, 35 miRNAs were found to negatively correlate with mRNA expression levels of 16 pharmacogenes in normal bile duct, liver, colon, and lung tissues (p<0.05). Additionally, 36 miRNAs were related to differential expression of 32 pharmacogene mRNAs in those normal and tumorigenic tissues (p<0.05). These results indicate that changes in expression levels of miRNAs targeted to pharmacogenes in normal and tumor tissues may play a role in determining individual variations in drug response.
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