Suppressor of cancer cell invasion (SCAI) acts as a transcriptional repressor of serum response factor (SRF)-mediated gene expression by binding to megakaryoblastic leukemia (MKL)/myocardin-related transcription factor (MRTF), which is an SRF transcriptional coactivator. Growing evidence suggests that SCAI is a negative regulator of neuronal morphology, whereas MKL2/MRTFB is a positive regulator. The mRNA expression of SCAI is downregulated during brain development, suggesting that a reduction in SCAI contributes to the reduced suppression of SRF-mediated gene induction, thus increasing dendritic complexity and developing neuronal circuits. In the present study, we hypothesized that brain-derived neurotrophic factor (BDNF), which is important for neuronal plasticity and development, might alter SCAI mRNA levels. We therefore investigated the effects of BDNF on SCAI mRNA levels in primary cultured cortical neurons. Furthermore, because alternative splicing generates several SCAI variants in the brain, we measured SCAI variant mRNA after BDNF stimulation. Both SCAI variant 1 and total SCAI mRNA expression levels were downregulated by BDNF. Moreover, the extracellular signal-regulated protein kinase/mitogen-activated protein kinase (ERK/MAPK) pathway was involved in the BDNF-mediated decrease in SCAI mRNA expression. Our findings provide insights into the molecular mechanism underlying a neurotrophic factor switch for the repressive transcriptional complex that includes SCAI.

中文翻译：

---

脑源性神经营养因子 (BDNF) 下调皮质神经元中癌细胞侵袭抑制因子 (SCAI) 变异的 mRNA 水平

癌细胞侵袭抑制因子 (SCAI) 通过与巨核细胞白血病 (MKL)/心肌素相关转录因子 (MRTF)（一种 SRF 转录共激活因子）结合，充当血清反应因子 (SRF) 介导的基因表达的转录抑制因子。越来越多的证据表明 SCAI 是神经元形态的负调节因子，而 MKL2/MRTFB 是正调节因子。SCAI的 mRNA 表达在大脑发育过程中下调，表明 SCAI 的减少有助于减少对 SRF 介导的基因诱导的抑制，从而增加树突的复杂性和发育神经元回路。在本研究中，我们假设脑源性神经营养因子 (BDNF) 对神经元可塑性和发育很重要，可能会改变SCAI mRNA 水平。因此，我们研究了 BDNF 对原代培养的皮质神经元SCAI mRNA 水平的影响。此外，由于选择性剪接在大脑中产生多种 SCAI 变体，因此我们在 BDNF 刺激后测量了SCAI变体 mRNA。SCAI变体 1 和总SCAI mRNA表达水平均被 BDNF 下调。此外，细胞外信号调节蛋白激酶/丝裂原激活蛋白激酶（ERK/MAPK）途径参与了 BDNF 介导的SCAI mRNA 表达下降。我们的研究结果提供了对包括SCAI在内的抑制性转录复合物的神经营养因子转换的分子机制的见解。