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Modulations of sirtuin 1 protein levels by nicotine and β‐ cryptoxanthin can be mediated by miR‐34a in A/J mice lung cancer model
Author(s) -
Iskandar Anita R,
You Min,
Wang XiangDong
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.32.2
Subject(s) - nicotine , sirtuin 1 , carcinogenesis , sirtuin , lung cancer , microrna , lung , endogeny , carcinogen , cancer research , chemistry , messenger rna , endocrinology , medicine , cancer , gene , downregulation and upregulation , biochemistry , acetylation
MicroRNAs (miRs) are small endogenous non‐coding RNAs that can regulate gene expression in a post‐transcriptional manner and target important molecules in carcinogenesis. We recently found that nicotine promoted lung tumorigenesis and emphysema in tobacco‐carcinogen (NNK)‐treated male A/J mice. We found that lung levels of sirtuin 1 (SIRT1) protein were decreased in the mice treated with the combination of NNK and nicotine. Moreover, β‐ cryptoxanthin (BCX) supplementation to these mice suppressed both lung tumor and emphysema development, which accompanied by SIRT1 protein restoration to normal levels without sirt1 mRNA alteration. This observation indicated a potential post‐transcriptional regulation of SIRT1. We then conducted real‐time PCR analyses to measure the lung levels of miR‐34a and miR‐217, which have been shown to hinder sirt1 translation. We observed that the levels of miR‐34a were increased in the lungs of the mice treated with the combination of NNK and nicotine, whereas miR‐217 levels were not different among all groups. The levels of miR‐34a in the lungs of the BCX‐supplemented mice were restored to that of the normal levels, indicating an inverse association between the levels of miR‐34a and SIRT1 protein. Our data indicate that the modulation of SIRT1 protein level by nicotine/BCX can be mediated by miR‐34a regulation in the nicotine‐promoted emphysema/lung tumorigenesis in A/J mice. Grant Funding Source : U.S. Department of Agriculture grant 1950–51000‐064S