LINC02282 promotes DNA methylation of TRIM6 by recruiting DNMTs to inhibit the progression of Parkinson's disease
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 mechanis...
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Elsevier
2025-03-01
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| Series: | Brain Research Bulletin |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S036192302500036X |
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| author | Lu Han Chuansheng Zhao Feng Jin Rongfeng Jiang Hao Wu |
| author_facet | Lu Han Chuansheng Zhao Feng Jin Rongfeng Jiang Hao Wu |
| author_sort | Lu Han |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-c2f35599d95945b39670ab04b9d5336e |
| institution | Kabale University |
| issn | 1873-2747 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
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| series | Brain Research Bulletin |
| spelling | doaj-art-c2f35599d95945b39670ab04b9d5336e2025-02-09T04:59:39ZengElsevierBrain Research Bulletin1873-27472025-03-01222111224LINC02282 promotes DNA methylation of TRIM6 by recruiting DNMTs to inhibit the progression of Parkinson's diseaseLu Han0Chuansheng Zhao1Feng Jin2Rongfeng Jiang3Hao Wu4Department of Neurology, Anshan Hospital, The First Hospital of China Medical University, Anshan, Liaoning 114000, PR China; Correspondence to: Department of Neurology, Anshan Hospital, The First Hospital of China Medical University, No. 166, Minzhu Street, Tiexi District, Anshan, Liaoning 114000, PR China.Department of Neurology, The First Hospital of China Medical University, Shenyang, Liaoning 110001, PR ChinaDepartment of Neurology, The First Hospital of China Medical University, Shenyang, Liaoning 110001, PR ChinaDepartment of orthopedics department, Anshan Hospital, The First Hospital of China Medical University, Anshan, Liaoning 114000, PR ChinaDepartment of orthopedics department, Anshan Hospital, The First Hospital of China Medical University, Anshan, Liaoning 114000, PR ChinaParkinson’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.http://www.sciencedirect.com/science/article/pii/S036192302500036XLINC02282TRIM6Parkinson's diseaseDNA methyltransferasesNeuronal injury |
| spellingShingle | Lu Han Chuansheng Zhao Feng Jin Rongfeng Jiang Hao Wu LINC02282 promotes DNA methylation of TRIM6 by recruiting DNMTs to inhibit the progression of Parkinson's disease Brain Research Bulletin LINC02282 TRIM6 Parkinson's disease DNA methyltransferases Neuronal injury |
| title | LINC02282 promotes DNA methylation of TRIM6 by recruiting DNMTs to inhibit the progression of Parkinson's disease |
| title_full | LINC02282 promotes DNA methylation of TRIM6 by recruiting DNMTs to inhibit the progression of Parkinson's disease |
| title_fullStr | LINC02282 promotes DNA methylation of TRIM6 by recruiting DNMTs to inhibit the progression of Parkinson's disease |
| title_full_unstemmed | LINC02282 promotes DNA methylation of TRIM6 by recruiting DNMTs to inhibit the progression of Parkinson's disease |
| title_short | LINC02282 promotes DNA methylation of TRIM6 by recruiting DNMTs to inhibit the progression of Parkinson's disease |
| title_sort | linc02282 promotes dna methylation of trim6 by recruiting dnmts to inhibit the progression of parkinson s disease |
| topic | LINC02282 TRIM6 Parkinson's disease DNA methyltransferases Neuronal injury |
| url | http://www.sciencedirect.com/science/article/pii/S036192302500036X |
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