Abstract Accumulating evidence suggests that dysregulation of long non-coding RNAs is closely associated with various human diseases, including Parkinson’s disease (PD). However, the role of nuclear-enriched abundant transcript 1 (NEAT1) in the PD process remains unclear. The number of TH+ cells was reduced, and the expression levels of NEAT1 and Krüppel-like factor 4 (KLF4) were increased in the midbrain of MPTP-HCl-treated mice. In addition, the expression of cleaved-caspase-3 (cleaved-casp-3) and Bax (apoptosis-related proteins) was increased, while the expression of Bcl-2 (anti-apoptotic protein) was reduced in MPTP-HCl-treated mice. The expression levels of NEAT1 and KLF4 were increased in MPP+-treated SH-SY5Y cells. Knockdown of NEAT1 promoted cell viability and decreased apoptosis in MPP+-treated SH-SY5Y cells, which could be reversed by upregulating KLF4. KLF4 was verified as a direct target of miR-124, and miR-124 could particularly bind to NEAT1. Downregulation of NEAT1 significantly increased cell viability and decreased apoptosis by regulating miR-124 expression in MPP+-treated SH-SY5Y cells. Additionally, interference of NEAT1 increased the number of TH+ cells and miR-124 expression, while reduced apoptosis and expression of KLF4 in vivo. NEAT1 knockdown increased cell viability and suppressed apoptosis in PD via regulating the miR-124/KLF4 axis, providing a promising avenue for the treatment of PD.

中文翻译：

---

帕金森病中长非编码RNA NEAT1通过调节miR-124/KLF4轴介导MPTP/MPP+诱导的细胞凋亡

摘要 越来越多的证据表明，长链非编码RNA的失调与多种人类疾病密切相关，包括帕金森病（PD）。然而，核富集丰富转录物 1 (NEAT1) 在 PD 过程中的作用仍不清楚。MPTP-HCl 处理的小鼠中脑中 TH+ 细胞数量减少，NEAT1 和 Krüppel 样因子 4 (KLF4) 的表达水平增加。此外，在MPTP-HCl处理中，cleaved-caspase-3（cleaved-casp-3）和Bax（凋亡相关蛋白）的表达增加，而Bcl-2（抗凋亡蛋白）的表达减少老鼠。MPP+处理的SH-SY5Y细胞中NEAT1和KLF4的表达水平增加。在 MPP+ 处理的 SH-SY5Y 细胞中，NEAT1 的敲低可促进细胞活力并减少细胞凋亡，这可以通过上调 KLF4 来逆转。KLF4被证实是miR-124的直接靶标，并且miR-124可以特异性地与NEAT1结合。在 MPP+ 处理的 SH-SY5Y 细胞中，NEAT1 的下调通过调节 miR-124 表达显着增加细胞活力并减少细胞凋亡。此外，干扰 NEAT1 会增加 TH+ 细胞的数量和 miR-124 的表达，同时减少体内细胞凋亡和 KLF4 的表达。NEAT1 敲除通过调节 miR-124/KLF4 轴增加 PD 细胞活力并抑制细胞凋亡，为 PD 治疗提供了一条有希望的途径。