Han Lu, Zhao Chuansheng, Jin Feng, Jiang Rongfeng, Wu Hao
Department of Neurology, Anshan Hospital, The First Hospital of China Medical University, Anshan, Liaoning 114000, PR China.
Department of Neurology, The First Hospital of China Medical University, Shenyang, Liaoning 110001, PR China.
Brain Res Bull. 2025 Mar;222:111224. doi: 10.1016/j.brainresbull.2025.111224. Epub 2025 Jan 30.
Parkinson's disease (PD) is the second most common neurodegenerative disease. Long non-coding RNAs (lncRNAs) are closely linked to the occurrence and development of neurodegenerative diseases, while the underlying mechanisms remain elusive. The goal of the present study was to elucidate the mechanism by which LINC02282, a significantly downregulated lncRNA in the GEO database, elicits neuroprotective effects on PD. LINC02282 was poorly expressed in SH-SY5Y and SK-N-AS cells exposed to MPP and mice injected with MPTP. LINC02282 overexpression plasmids inhibited apoptosis and promoted the proliferation of SH-SY5Y and SK-N-AS cells. In addition, LINC02282 overexpression using an adeno-associated virus reduced neuronal damage in PD mice. LINC02282 was mainly localized in the nucleus, and LINC02282 promoted the methylation of the tripartite motif-containing protein 6 (TRIM6) promoter to inhibit TRIM6 expression. LINC02282 bound to DNA methyltransferases (DNMTs) and LINC02282 overexpression increased the binding of DNMTs to the TRIM6 promoter. Overexpression of TRIM6 alone induced PD-like symptoms in mice and combined TRIM6 upregulation inhibited the neuroprotective effect of LINC02282 both in vitro and in vivo. In summary, LINC02282 alleviated neuronal injury in PD by recruiting DNMTs to the promoter region of TRIM6 and inhibiting TRIM6 expression.
帕金森病（PD）是第二常见的神经退行性疾病。长链非编码RNA（lncRNAs）与神经退行性疾病的发生和发展密切相关，但其潜在机制仍不清楚。本研究的目的是阐明GEO数据库中显著下调的lncRNA LINC02282对PD产生神经保护作用的机制。在暴露于MPP的SH-SY5Y和SK-N-AS细胞以及注射MPTP的小鼠中，LINC02282表达较低。LINC02282过表达质粒抑制了SH-SY5Y和SK-N-AS细胞凋亡并促进其增殖。此外，使用腺相关病毒过表达LINC02282可减少PD小鼠的神经元损伤。LINC02282主要定位于细胞核，且LINC02282促进含三联基序蛋白6（TRIM6）启动子的甲基化以抑制TRIM6表达。LINC02282与DNA甲基转移酶（DNMTs）结合，LINC02282过表达增加了DNMTs与TRIM6启动子的结合。单独过表达TRIM6可在小鼠中诱导PD样症状，且联合上调TRIM6可在体外和体内抑制LINC02282的神经保护作用。总之，LINC02282通过将DNMTs募集到TRIM6启动子区域并抑制TRIM6表达来减轻PD中的神经元损伤。
