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

Publication ,  Journal Article
Gordon, MW; Yan, F; Zhong, X; Mazumder, PB; Xu-Monette, ZY; Zou, D; Young, KH; Ramos, KS; Li, Y
Published in: Mol Carcinog
October 2015

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.

Duke Scholars

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Published In

Mol Carcinog

DOI

EISSN

1098-2744

Publication Date

October 2015

Volume

54

Issue

10

Start / End Page

1060 / 1069

Location

United States

Related Subject Headings

  • Up-Regulation
  • Tumor Suppressor Protein p53
  • Receptors, Aryl Hydrocarbon
  • Promoter Regions, Genetic
  • Polycyclic Aromatic Hydrocarbons
  • Oncology & Carcinogenesis
  • Multiple Myeloma
  • MicroRNAs
  • Humans
  • Hela Cells
 

Citation

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MLA
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Gordon, M. W., Yan, F., Zhong, X., Mazumder, P. B., Xu-Monette, Z. Y., Zou, D., … Li, Y. (2015). Regulation of p53-targeting microRNAs by polycyclic aromatic hydrocarbons: Implications in the etiology of multiple myeloma. Mol Carcinog, 54(10), 1060–1069. https://doi.org/10.1002/mc.22175
Gordon, Michael W., Fang Yan, Xiaoming Zhong, Pranab Behari Mazumder, Zijun Y. Xu-Monette, Dehui Zou, Ken H. Young, Kenneth S. Ramos, and Yong Li. “Regulation of p53-targeting microRNAs by polycyclic aromatic hydrocarbons: Implications in the etiology of multiple myeloma.Mol Carcinog 54, no. 10 (October 2015): 1060–69. https://doi.org/10.1002/mc.22175.
Gordon MW, Yan F, Zhong X, Mazumder PB, Xu-Monette ZY, Zou D, et al. Regulation of p53-targeting microRNAs by polycyclic aromatic hydrocarbons: Implications in the etiology of multiple myeloma. Mol Carcinog. 2015 Oct;54(10):1060–9.
Gordon, Michael W., et al. “Regulation of p53-targeting microRNAs by polycyclic aromatic hydrocarbons: Implications in the etiology of multiple myeloma.Mol Carcinog, vol. 54, no. 10, Oct. 2015, pp. 1060–69. Pubmed, doi:10.1002/mc.22175.
Gordon MW, Yan F, Zhong X, Mazumder PB, Xu-Monette ZY, Zou D, Young KH, Ramos KS, Li Y. Regulation of p53-targeting microRNAs by polycyclic aromatic hydrocarbons: Implications in the etiology of multiple myeloma. Mol Carcinog. 2015 Oct;54(10):1060–1069.
Journal cover image

Published In

Mol Carcinog

DOI

EISSN

1098-2744

Publication Date

October 2015

Volume

54

Issue

10

Start / End Page

1060 / 1069

Location

United States

Related Subject Headings

  • Up-Regulation
  • Tumor Suppressor Protein p53
  • Receptors, Aryl Hydrocarbon
  • Promoter Regions, Genetic
  • Polycyclic Aromatic Hydrocarbons
  • Oncology & Carcinogenesis
  • Multiple Myeloma
  • MicroRNAs
  • Humans
  • Hela Cells