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FTO基因通过相似机制影响肥胖和乳腺癌:对分子治疗靶点的新见解

FTO Gene Affects Obesity and Breast Cancer Through Similar Mechanisms: A New Insight into the Molecular Therapeutic Targets.

作者信息

Akbari M E, Gholamalizadeh M, Doaei S, Mirsafa F

机构信息

a Cancer Research Center (CRC), Shahid Beheshti University of Medical Sciences , Tehran , Iran.

b Student Research Committee, Cancer Research Center , Shahid Beheshti University of Medical Sciences , Tehran , Iran.

出版信息

Nutr Cancer. 2018 Jan;70(1):30-36. doi: 10.1080/01635581.2018.1397709. Epub 2017 Dec 8.

Abstract

OBJECTIVES

This review focused on the possible mediatory role of the FTO in the association between obesity and breast cancer.

METHOD

All articles published in English from June 1990 to January 2017 were studied. The search terms used were FTO gene, FTO polymorphism, breast cancer, and obesity. Inclusion criteria consisted of assessment of the relationship between FTO polymorphisms and/or FTO expression level with obesity and/or breast cancer as a primary outcome.

RESULTS

The FTO gene may have a role in the cellular sensing of macronutrients. Over expression of the FTO gene increases the levels of mammalian target of rapamycin (mTOR) signaling that is a key regulator of cell growth. Moreover, some SNPs in intron locations of the FTO gene exert their effects on body mass index, body composition and breast cancer risk through change of the homeobox transcription factor iriquois 3 (IRX3) gene expression level.

CONCLUSION

The FTO gene may has a critical role in obesity and breast cancer. Similar molecular mechanisms may play a role in the development of breast cancer and obesity. If this result is correct then, it will be interesting to examine the FTO gene as a molecular therapeutics target.

摘要

目的

本综述聚焦于FTO基因在肥胖与乳腺癌关联中可能的中介作用。

方法

研究了1990年6月至2017年1月以英文发表的所有文章。使用的检索词为FTO基因、FTO多态性、乳腺癌和肥胖。纳入标准包括以FTO多态性和/或FTO表达水平与肥胖和/或乳腺癌之间的关系评估作为主要结果。

结果

FTO基因可能在对大量营养素的细胞感知中发挥作用。FTO基因的过表达会增加雷帕霉素哺乳动物靶标(mTOR)信号传导水平,而mTOR信号传导是细胞生长的关键调节因子。此外,FTO基因内含子位置的一些单核苷酸多态性(SNP)通过改变同源盒转录因子Iriquois 3(IRX3)基因表达水平,对体重指数、身体成分和乳腺癌风险产生影响。

结论

FTO基因可能在肥胖和乳腺癌中起关键作用。相似的分子机制可能在乳腺癌和肥胖的发生发展中发挥作用。如果这一结果正确,那么将FTO基因作为分子治疗靶点进行研究将会很有意思。

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