Format

Send to

Choose Destination
J Nutr Biochem. 2019 Mar 28;68:69-78. doi: 10.1016/j.jnutbio.2019.03.011. [Epub ahead of print]

CpG methyl-seq and RNA-seq epigenomic and transcriptomic studies on the preventive effects of Moringa isothiocyanate in mouse epidermal JB6 cells induced by the tumor promoter TPA.

Author information

1
Center for Phytochemical Epigenome Studies, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA; Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
2
Center for Phytochemical Epigenome Studies, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA; Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA; Graduate Program of Pharmaceutical Sciences, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
3
Department of Statistics and Biostatistics, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
4
Department of Plant Biology & Pathology, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901, USA.
5
Center for Phytochemical Epigenome Studies, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA; Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA. Electronic address: KongT@pharmacy.rutgers.edu.

Abstract

Epigenetic mechanisms play an important role in the early stages of carcinogenesis. Moringa isothiocyanate (MIC-1) is a major bioactive component derived from Moringa oleifera that has considerable antioxidant and anti-inflammatory effects. However, how MIC-1 influences epigenomic alterations in TPA-mediated JB6 cell carcinogenic transformation has not been evaluated. In this study, DNA and RNA isolated from TPA-induced JB6 cells in the presence or absence of MIC-1 were subjected to DNA Methyl-seq and RNA-seq to identify differentially methylated regions (DMRs) and differentially expressed genes (DEGs), respectively. When JB6 cells were challenged with TPA alone, there was a significant alteration of DEGs and DMRs; importantly, MIC-1 treatment reversed the patterns of some of the DEGs and DMRs. Transcriptome and CpG methylome profiling was performed in Ingenuity® Pathway Analysis (IPA) software to analyze the altered signaling pathways. Several anti-inflammatory responses, antioxidative stress-related pathways, and anticancer-related pathways were identified to be affected by MIC-1. These pathways included NF-kB, IL-1, LPS/IL-1-mediated inhibition of RXR function, Nrf2-mediated oxidative stress response, p53, and PTEN signaling pathways. Examination of correlations between transcriptomic and CpG methylome profiles yielded a small subset of genes, including the cancer-related genes Tmpt, Tubb3, and Muc2; the GTPases Gchfr and Igtp; and the cell cycle-related gene Cdc7. Taken together, our results show the potential contributions of epigenomic changes in DNA CpG methylation to gene expression to molecular pathways active in TPA-induced JB6 cells and demonstrate that MIC-1 can reverse these changes, supporting the potential preventive/treatment effects of MIC-1 against skin carcinogenesis.

KEYWORDS:

DNA methylome; JB6 Cell; Moringa isothiocyanate; TPA; Transcriptome

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center