Format

Send to

Choose Destination
See comment in PubMed Commons below
Mol Carcinog. 2015 Oct;54(10):1060-9. doi: 10.1002/mc.22175. Epub 2014 May 6.

Regulation of p53-targeting microRNAs by polycyclic aromatic hydrocarbons: Implications in the etiology of multiple myeloma.

Author information

  • 1Department of Biochemistry and Molecular Biology, School of Medicine, University of Louisville, Louisville, Kentucky.
  • 2Department of Histology and Embryology, Southern Medical University, Guangzhou, Guangdong, China.
  • 3Department of Cardiology, Huaihe Hospital of Henan University, Kaifeng, Henan, China.
  • 4Department of Biotechnology, Assam University, Silchar, Assam, India.
  • 5Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.

Abstract

Multiple myeloma (MM) is a common and deadly cancer of blood plasma cells. A unique feature of MM is the extremely low somatic mutation rate of the p53 tumor suppressor gene, in sharp contrast with about half of all human cancers where this gene is frequently mutated. Eleven miRNAs have been reported to repress p53 through direct interaction with the 3' untranslated region. The expression of nine of them is higher in MM plasma cells than in healthy donor counterparts, suggesting that miRNA overexpression is responsible for p53 inactivation in MM. Here, we report that the environmental carcinogen benzo[a]pyrene (BaP) upregulated the expression of seven p53-targeting miRNAs (miR-25, miR-15a, miR-16, miR-92, miR-125b, miR-141, and miR-200a), while 2,3,7,8-tetrachlorodibenzo-ρ-dioxin (TCDD) upregulated two of them (miR-25 and miR-92) in MM cells. The miR-25 promoter was activated by both BaP and TCDD, and this response was mediated by the aryl hydrocarbon receptor (AhR). We screened 727 compounds that inhibit MM cell survival and down-regulate the expression of p53-targeting miRNAs. We found that (-)-epigallocatechin-3-gallate (EGCG), a constituent of green tea and a major component of the botanical drug Polyphenon® E, reduced the expression of four p53-targeting miRNAs, including miR-25, miR-92, miR-141, and miR-200a. Collectively, these data implicate polycyclic aromatic hydrocarbons and AhR in the regulation of p53-targeting miRNAs in MM and identify a potential therapeutic and preventive agent to combat this deadly disease.

© 2014 Wiley Periodicals, Inc.

KEYWORDS:

microRNAs; multiple myeloma; p53; polycyclic aromatic hydrocarbons; toxicants

PMID:
24798859
PMCID:
PMC4223015
[Available on 2016-10-01]
DOI:
10.1002/mc.22175
[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Wiley
    Loading ...
    Write to the Help Desk