Hypoxia decreases macrophage glycolysis and M1 percentage by targeting microRNA‐30c and mTOR in human gastric cancer

摘要

Macrophages are essential inflammatory cells which regulate the features of immune reactions within tumors. Many studies have reported their regulatory roles in immunity through cytokines and cell signaling. However, relatively few studies have focused on their metabolic features and mechanisms. We aimed to determine the signaling pathway regulating cell metabolism and the mechanism related to the regulation of human tumor‐associated macrophages ( s) in gastric cancer ( ). Tumor‐infiltrated macrophages were isolated from human tissues using magnetic beads, gene transcription was determined by real‐time , protein expression was monitored using western blots, metabolites were determined using , and transcriptional regulation was analyzed by the luciferase‐based reporter gene system. A significant decrease in microRNA (miR)‐30c and an increase in regulated in development and DNA damage responses 1 (REDD1) were detected in human s, the transcription of miR‐30c was negatively correlated with 1. MicroRNA‐30c expression was suppressed by hypoxia‐inducible factor‐1α activation and related to decreased activity as well as glycolysis in human s. Hypoxia‐regulated miR‐30c downregulated ‐1 expression by targeting its 3′ . Overexpression of miR‐30c or restored activity in macrophages with miR‐30c expression promoted M1 macrophage differentiation and function in s. Therefore, hypoxia in the human microenvironment suppressed the expression of miR‐30c, and decreased activity as well as glycolysis in s, thus inhibiting M1 differentiation and function. These results provide a novel metabolic strategy for tumor microenvironment‐based therapy.