A regulation loop between Nrf1 alpha and MRTF-A controls migration and invasion in MDA-MB-231 breast cancer cells

作者：Xu, Yao; Luo, Ying; Liang, Chen; Xing, Weibing^*; Zhang, Tongcun^*

来源：International Journal of Molecular Medicine, 2018, 42(5): 2459-2468.

DOI：10.3892/ijmm.2018.3816

• myocardin-related transcription factor A
• nuclear factor erythroid 2-like 1
• breast cancer
• migration
• invasion

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 Nrf1 (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, Nrf1 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 Nrf1 expression through binding to the CarG box in the Nrf1 promoter. It can be speculated that this regulation loop may be a homeostasis mechanism in cells against tumorigenesis.

• 出版日期2018-11
• 单位武汉科技大学