miR-328 mediates a metabolic shift in colon cancer cells by targeting SLC2A1/GLUT1

Abstract

Purpose: Increasing evidence shows that altered metabolism is a critical hallmark in colon cancer. There is a strong need to explore the molecular mechanisms underlying cancer metabolism. Whether the aberrant expression of microRNAs contributes to cancer metabolism is not fully understood. miR-328 is a putative potential target of SLC2A1, but the regulating mechanism between them remains unknown. We have examined whether miR-328 directly regulates SLC2A1/GLUT1 expression in colon cancer cells. Methods: We performed in silico bioinformatic analyses to identify miR-328-mediated molecular pathways and targets. We also performed luciferase assays and western blot analyses in LOVO and SW480 colon cancer cell lines. In addition, we assessed miR-328 expression in 47 paired tumor and normal tissue specimens from resected colon cancer patients. Results: Luciferase reporter assays showed that miR-328 directly targeted SLC2A1 3′-untranslated region (UTR), with a significant decrease in luciferase activity in both LOVO and SW480 cell lines. These results were validated by western blot. miR-328 expression was significantly downregulated in tumor tissue compared with paired normal tissue. Conclusions: Our results show that miR-328 targets SLC2A1/GLUT1. We suggest that miR-328 may be involved in the orchestration of the Warburg effect in colon cancer cells. Furthermore, miR‐328 expression is reduced in colon cancer patients and thus inversely correlates with the classically reported upregulated SLC2A1/GLUT1 expression in tumors.