The miR-27a/FOXJ3 Axis Dysregulates Mitochondrial Homeostasis in Colorectal Cancer Cells

Cellular and mitochondrial metabolism can be dysregulated during tumorigenesis. miR-27a plays a central role in redirecting cell metabolism in colorectal cancer. In this study, we searched for new miR-27a targets that could influence mitochondria and identified FOXJ3 a master regulator of mitochondrial biogenesis. We validated FOXJ3 as an miR-27a target in an in vitro cell model system that was genetically modified for miR-27a expression and showed that the miR-27a/FOXJ3 axis down-modulates mitochondrial biogenesis and regulates other members of the pathway. The miR-27a/FOXJ3 axis also influences mitochondrial dynamics, superoxide production, respiration capacity, and membrane potential. A mouse xenograft model confirmed that miR-27a downregulates FOXJ3 in vivo and a survey of the TCGA-COADREAD dataset supported the inverse relationship of FOXJ3 with miR-27a and the impact on mitochondrial biogenesis. The miR-27a/FOXJ3 axis is a major actor in regulating mitochondrial homeostasis, and its discovery may contribute to therapeutic strategies aimed at restraining tumor growth by targeting mitochondrial activities.