Distinct perturbation of the translatome by the antidiabetic drug metformin

作者：Larsson Ola; Morita Masahiro; Topisirovic Ivan; Alain Tommy; Blouin Marie Jose; Pollak Michael^*; Sonenberg Nahum

来源：Proceedings of the National Academy of Sciences, 2012, 109(23): 8977-8982.

DOI：10.1073/pnas.1201689109

• polysome-microarray
• posttranscriptional regulation
• translatomics

Metformin has been reported to lower cancer incidence among type II diabetics. Metformin exhibits antiproliferative and antineoplastic effects associated with inhibition of mammalian target of rapamycin complex 1 (mTORC1), but the mechanisms are poorly understood. We provide a unique genome-wide analysis of translational targets of canonical mTOR inhibitors (rapamycin and PP242) compared with metformin, revealing that metformin controls gene expression at the level of mRNA translation to an extent comparable to that of canonical mTOR inhibitors. Importantly, metformin's antiproliferative activity can be explained by selective translational suppression of mRNAs encoding cell-cycle regulators via the mTORC1/eukaryotic translation initiation factor 4E-binding protein pathway. Thus, metformin selectively inhibits translation of mRNAs encoding proteins that promote neoplastic proliferation, which should facilitate studies on metformin and related biguanides in cancer prevention and treatment.

• 出版日期2012-6-5
• 单位河北医科大学