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

作者：Kim Sinae; Lee Eunji; Jung Jaeyun; Lee Jong Won; Kim Hee Jung; Kim Jisun; Yoo Hyun ju; Lee Hee Jin; Chae Sun Young; Jeon Sang Min; Son Byung Ho; Gong Gyungyup; Sharan Shyam K; Chang Suhwan^*

来源：Oncogene, 2018, 37(22): 2982-2991.

DOI：10.1038/s41388-018-0124-4

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.

• 出版日期2018-5