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.