A regulation loop between Nrf1α and MRTF-A controls migration and invasion in MDA-MB-231 breast cancer cells

As a strong transactivator of promoters containing CarG boxes, myocardin-related transcription factor A (MRTF-A) is critical for the process of metastasis in tumor cells. Nuclear factor erythroid 2-like 1 (Nrf1) is well known as an important regulator of oxidative stress, which exists in multiple splicing forms with many unknown functions. The present study demonstrated a novel regulation loop between Nrf1α (the longest splicing form of Nrf1) and MRTF-A that regulated the migration and invasion of breast cancer MDA-MB-231 cells. The underlying mechanism of this regulation look was further investigated. In particular, Nrf1α inhibited migration and invasion of breast cancer cells through inhibiting the expression of MRTF-A via miR-219. The current results revealed that miR-219 could bind to the MRTF-A 3′-UTR to directly regulate its expression. However, MRTF-A could reverse activate the Nrf1α expression through binding to the CarG box in the Nrf1α promoter. It can be speculated that this regulation loop may be a homeostasis mechanism in cells against tumorigenesis.