Prior evidence has suggested the alleviatory effect of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) on neuroinflammation in neurodegenerative diseases. This study primarily investigates the underlying mechanism of how the long non-coding RNA MALAT1 affects neuronal apoptosis in the hippocampus of mice with autism spectrum disorder (ASD). The findings demonstrate that CASP3 is highly expressed while MALAT1 is downregulated in the hippocampal neurons of autistic mice. MALAT1 mainly localizes within the cell nucleus and recruits DNA methyltransferases (including DNMT1, DNMT3a, and DNMT3b) to the promoter region of CASP3, promoting its methylation and further inhibiting its expression. In vitro experiments reveal that reducing MALAT1 expression promotes the expression of CASP3 and Bax while suppressing Bcl-2 expression, thereby enhancing cellular apoptosis. Conversely, increasing MALAT1 expression yields the opposite effect. Consequently, these results further confirm the role of MALAT1 in suppressing neuronal apoptosis in the hippocampus of mice with ASD through the regulation of CASP3 promoter methylation. Thus, this research unveils the significant roles of MALAT1 and CASP3 in the pathogenesis of ASD, offering new possibilities for future therapeutic interventions.

先前的证据表明转移相关肺腺癌转录物 1 (MALAT1) 对神经退行性疾病中的神经炎症有缓解作用。本研究主要探讨长链非编码RNA MALAT1如何影响自闭症谱系障碍（ASD）小鼠海马神经元凋亡的潜在机制。研究结果表明，自闭症小鼠的海马神经元中 CASP3 高表达，而 MALAT1 下调。MALAT1主要定位于细胞核内，将DNA甲基转移酶（包括DNMT1、DNMT3a和DNMT3b）招募到CASP3的启动子区域，促进其甲基化并进一步抑制其表达。体外实验表明，减少MALAT1的表达可以促进CASP3和Bax的表达，同时抑制Bcl-2的表达，从而增强细胞凋亡。相反，增加 MALAT1 表达会产生相反的效果。因此，这些结果进一步证实了MALAT1通过调节CASP3启动子甲基化抑制ASD小鼠海马神经元凋亡的作用。因此，这项研究揭示了 MALAT1 和 CASP3 在 ASD 发病机制中的重要作用，为未来的治疗干预提供了新的可能性。