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Oncogene. 2018 May;37(22):2982-2991. doi: 10.1038/s41388-018-0124-4. Epub 2018 Mar 12.

microRNA-155 positively regulates glucose metabolism via PIK3R1-FOXO3a-cMYC axis in breast cancer.

Author information

1
Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul, 05505, Korea.
2
Department of Surgery, Asan Medical Center, Seoul, 05505, Korea.
3
Department of Convergence Medicine, University of Ulsan College of Medicine, Seoul, 05505, Korea.
4
Department of Pathology, Asan Medical Center, Seoul, 05505, Korea.
5
Department of Nuclear Medicine, Asan Medical Center, Seoul, 05505, Korea.
6
College of Pharmacy and Institute of Pharmaceutical Science and Technology, Ajou University, Suwon, 16499, Korea.
7
Mouse Cancer Genetics Program, Frederick National Laboratory, Frederick, MD, 21702, USA.
8
Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul, 05505, Korea. suhwan.chang@amc.seoul.kr.

Abstract

MicroRNA is an endogenous, small RNA controlling multiple target genes and playing roles in various biological processes including tumorigenesis. Here, we addressed the function of miR-155 using LC-MS/MS-based metabolic profiling of miR-155 deficient breast cancer cells. Our results revealed the loss of miR-155 hampers glucose uptake and glycolysis, via the down-regulation of glucose transporters and metabolic enzymes including HK2, PKM2, and LDHA. We showed this is due to the down-regulation of cMYC, controlled through phosphoinositide-3-kinase regulatory subunit alpha (PIK3R1)-PDK1/AKT-FOXO3a pathway. UTR analysis of the PIK3R1 and FOXO3a indicated miR-155 directly represses these genes. A stable expression of miR-155 in patient-derived cells (PDCs) showed activated glucose metabolism whereas a stable inhibition of miR-155 reduced in vivo tumor growth with retarded glucose metabolism. Furthermore, analysis of 50 triple-negative breast cancer (TNBC) specimens and specific uptake value (SUV) of PET images revealed a positive correlation between miR-155 level and glucose usage in human breast tumors via PIK3R1-PDK/AKT-FOXO3a-cMYC axis. Collectively, these data demonstrate the miR-155 is a key regulator of glucose metabolism in breast cancer.

PMID:
29527004
PMCID:
PMC5978802
DOI:
10.1038/s41388-018-0124-4
[Indexed for MEDLINE]
Free PMC Article

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