Identification of Potential Target Genes of Butyrate in Dimethylhydrazine-Induced Colorectal Cancer in Mice

Abstract

The mechanism by which butyrate prevents colorectal cancer (CRC) is unclear. The objective of this study was to identify potential target genes of butyrate in 1,2-dimethylhydrazine (DMH)-induced CRC in mice. Nontumor colorectal tissues of mice from DMH + butyrate, DMH, and control groups were hybridized on Agilent Mouse Whole Genome 44K Oligo Microarrays. Selected genes were validated by qRT-PCR. Data was further analyzed by KEGG, gene ontology (GO), and pathway studio software. The tumor incidence in the DMH + butyrate and DMH groups was 30% and 90%, respectively (P < 0.05). There were 355 genes downregulated due to DMH treatment while upregulated by butyrate, and 475 genes upregulated by DMH while downregulated by butyrate. The results revealed that most of the tumor-related signaling pathways (e.g., MAPK pathway, Wnt pathway, insulin pathway, and VEGF pathway) were downregulated by butyrate. The GO terms related to cell differentiation, cell cycle, cell proliferation, cell death, cell adhesion, and cell migration were significantly affected. The chemopreventive effects of butyrate were confirmed in the DMH-induced CRC mice model. And mechanisms encompassing multiple pathways and GO terms are involved in the regulation of gene expression.

ACKNOWLEDGMENTS

We thank Dr. Xiao-Yu Chen, Qi Miao, Yun Cui, Wei-Qi Gu and Hong-Yin Zhu for their excellent technical assistance. Hui-Min Chen and Yan-Wei Lin contributed equally to this work. This work was supported by grants from the Ministry of Public Health, China (No. 200802094), the Ministry of Education, China (No. 20090073110077) to Jing-Yuan Fang, Shanghai Jiao-Tong University School of Medicine Foundation for Science and Technology (No. BXJ0914) to Hui-Min Chen, the Scholarship Award for Excellent Doctoral Student Granted by Ministry of Education to Hui-Min Chen, and the National Science Found of China (30830055). This work was also supported by grants from 2012 special fund of Shanghai Universities for Outstanding Young Teachers Training (101005.001.14.100), the Research Project of Shanghai Science and Technology Commission (12ZR1446200) and the funded project of Chinese National Science Fund Committee (81201911). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Series record of GEO: GSE25858. For information on GEO linking and citing, please refer to http://www.ncbi.nlm.nih.gov/geo/info/linking.html.