A regulation loop between Nrf1α and MRTF-A controls migration and invasion in MDA-MB-231 breast cancer cells.
A regulation loop between Nrf1α and MRTF-A controls migration and invasion in MDA-MB-231 breast cancer cells.
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Nrf1 和 MRTF-A 之间的调节环控制 MDA-MB-231 乳腺癌细胞的迁移和侵袭
DOI：
10.3892/ijmm.2018.3816
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发表时间：
2018-11
影响因子：
5.4
通讯作者：
Zhang T
中科院分区：
文献类型：
--
作者：
Xu Y;Luo Y;Liang C;Xing W;Zhang T
心肌素相关转录因子a （MRTF-A）作为含有CarG盒的启动子的强反激活因子，在肿瘤细胞转移过程中起着至关重要的作用。核因子红细胞2样1 （Nrf1）作为氧化应激的重要调控因子，以多种剪接形式存在，功能未知。本研究证实了Nrf1α （Nrf1的最长剪接形式）和MRTF-A之间存在一种新的调控环，可调节乳腺癌MDA-MB-231细胞的迁移和侵袭。进一步研究了这种调控的潜在机制。特别是Nrf1α通过miR-219抑制MRTF-A的表达，从而抑制乳腺癌细胞的迁移和侵袭。目前的研究结果表明，miR-219可以结合MRTF-A 3 ' -UTR直接调控其表达。然而，MRTF-A可以通过结合Nrf1α启动子中的CarG盒子来逆转Nrf1α的表达。可以推测，这种调控回路可能是细胞抗肿瘤发生的一种稳态机制。
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.
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