Breast cancer is the most common cancer for women worldwide. Although the oncogenic roles of miR-155 in cancer have been reported, the metabolic function of miR-155 in breast cancer has not been fully elucidated. In this study, we have investigated how the energy metabolic shift occurs after a genetic inactivation or knockdown of miR-155. To this end, we performed metabolic profiling of the miR-155ko/ko or miR-155+/ko primary cancer cells, obtained from mouse breast cancer model. We found, in the absence of miR-155, less glucose uptake and glycolysis in tumor cells. Mechanistically, we revealed PIK3R1(Phosphoinositide-3-Kinase, Regulatory Subunit1, p85<alpha>) and FOXO3a (Forkhead transcription factor of the O class 3a) are major targets that trigger the metabolic shift. Furthermore, we showed cMYC level was consequently decreased in the absence of miR-155 that results in the down-regulation of proteins playing in glucose uptake and Glycolysis. This finding is further confirmed in mouse allograft model. Finally, we show the miR-155 expression is positively correlates with either energy metabolite levels or standardized uptake values (SUV) of fluoro-deoxy glucose (FDG)-PET Images in triple negative breast tumors. Taken together, our study demonstrates a novel mechanism by which the miR-155 controls energy metabolism in breast cancer, through PI3K p85<alpha>-FOXO3a-cMYC axis.

Citation Format: Sinae Kim, Eunji Lee, Suhwan Chang. miR-155 positively regulates glucose metabolism via PI3K p85<alpha>-FOXO3a-cMYC axis in breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3557. doi:10.1158/1538-7445.AM2017-3557

©2017 American Association for Cancer Research.
2017
American Association for Cancer Research.