Department of Biochemistry & Molecular Biology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou City, China.
RNA Biol. 2013 Apr;10(4):465-80. doi: 10.4161/rna.24370. Epub 2013 Apr 1.
GATA-4 is an important transcription factor involved in several developmental processes of the heart, such as cardiac myocyte proliferation, differentiation and survival. The precise mechanisms underlying the regulation of GATA-4 remain unclear, this is especially true for the mechanisms that mediate the post-transcriptional regulation of GATA-4. Here, we demonstrate that miR-200b, a member of the miR-200 family, is a critical regulator of GATA-4. Overexpression of miR-200b leads to the downregulation of GATA-4 mRNA and a decrease in GATA-4 protein levels. Moreover, miR-200b not only inhibits cell growth and differentiation but also reverses the growth response mediated by GATA-4, whereas depletion of miR-200b leads to a slight reversal of the anti-growth response achieved by knocking down endogenous GATA-4. More importantly, the cell cycle-associated gene cyclin D1, which is a downstream target of GATA-4, is also regulated by miR-200b. Thus, miR-200b targets GATA-4 to downregulate the expression of cyclin D1 and myosin heavy chain (MHC), thereby regulating cell growth and differentiation.
GATA-4 是一种重要的转录因子，参与心脏的几个发育过程，如心肌细胞增殖、分化和存活。GATA-4 调节的确切机制尚不清楚，特别是介导 GATA-4 转录后调节的机制。在这里，我们证明 miR-200b，miR-200 家族的一员，是 GATA-4 的关键调节因子。miR-200b 的过表达导致 GATA-4 mRNA 的下调和 GATA-4 蛋白水平的降低。此外，miR-200b 不仅抑制细胞生长和分化，而且逆转由 GATA-4 介导的生长反应，而 miR-200b 的耗竭导致敲低内源性 GATA-4 所获得的抗生长反应略有逆转。更重要的是，细胞周期相关基因 cyclin D1，它是 GATA-4 的下游靶标，也受到 miR-200b 的调节。因此，miR-200b 靶向 GATA-4 下调 cyclin D1 和肌球蛋白重链 (MHC) 的表达，从而调节细胞生长和分化。
