Characterizing Relevant MicroRNA Editing Sites in Parkinson’s Disease
MicroRNAs (miRNAs) are extensively edited in human brains. However, the functional relevance of the miRNA editome is largely unknown in Parkinson’s disease (PD). By analyzing small RNA sequencing profiles of brain tissues of 43 PD patients and 88 normal controls, we found that the editing levels of...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-12-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/12/1/75 |
| _version_ | 1797626145712111616 |
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| author | Chenyu Lu Shuchao Ren Wenping Xie Zhigang Zhao Xingwang Wu Shiyong Guo Angbaji Suo Nan Zhou Jun Yang Shuai Wu Yun Zheng |
| author_facet | Chenyu Lu Shuchao Ren Wenping Xie Zhigang Zhao Xingwang Wu Shiyong Guo Angbaji Suo Nan Zhou Jun Yang Shuai Wu Yun Zheng |
| author_sort | Chenyu Lu |
| collection | DOAJ |
| description | MicroRNAs (miRNAs) are extensively edited in human brains. However, the functional relevance of the miRNA editome is largely unknown in Parkinson’s disease (PD). By analyzing small RNA sequencing profiles of brain tissues of 43 PD patients and 88 normal controls, we found that the editing levels of five A-to-I and two C-to-U editing sites are significantly correlated with the ages of normal controls, which is disrupted in PD patients. We totally identified 362 miRNA editing sites with significantly different editing levels in prefrontal cortices of PD patients (PD-PC) compared to results of normal controls. We experimentally validated that A-to-I edited miR-497-5p, with significantly higher expression levels in PD-PC compared to normal controls, directly represses OPA1 and VAPB. Furthermore, overexpression of A-to-I edited miR-497-5p downregulates OPA1 and VAPB in two cell lines, and inhibits proliferation of glioma cells. These results suggest that the hyperediting of miR-497-5p in PD contributes to enhanced progressive neurodegeneration of PD patients. Our results provide new insights into the mechanistic understanding, novel diagnostics, and therapeutic clues of PD. |
| first_indexed | 2024-03-11T10:06:20Z |
| format | Article |
| id | doaj.art-e16a1bf982ad42cca9051675f24ed960 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-11T10:06:20Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-e16a1bf982ad42cca9051675f24ed9602023-11-16T15:05:44ZengMDPI AGCells2073-44092022-12-011217510.3390/cells12010075Characterizing Relevant MicroRNA Editing Sites in Parkinson’s DiseaseChenyu Lu0Shuchao Ren1Wenping Xie2Zhigang Zhao3Xingwang Wu4Shiyong Guo5Angbaji Suo6Nan Zhou7Jun Yang8Shuai Wu9Yun Zheng10College of Landscape and Horticulture, Yunnan Agricultural University, Kunming 650201, ChinaCollege of Landscape and Horticulture, Yunnan Agricultural University, Kunming 650201, ChinaFaculty of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, ChinaCollege of Landscape and Horticulture, Yunnan Agricultural University, Kunming 650201, ChinaCollege of Landscape and Horticulture, Yunnan Agricultural University, Kunming 650201, ChinaCollege of Landscape and Horticulture, Yunnan Agricultural University, Kunming 650201, ChinaCollege of Landscape and Horticulture, Yunnan Agricultural University, Kunming 650201, ChinaCollege of Landscape and Horticulture, Yunnan Agricultural University, Kunming 650201, ChinaSchool of Criminal Investigation, Yunnan Police College, Kunming 650223, ChinaCollege of Landscape and Horticulture, Yunnan Agricultural University, Kunming 650201, ChinaCollege of Landscape and Horticulture, Yunnan Agricultural University, Kunming 650201, ChinaMicroRNAs (miRNAs) are extensively edited in human brains. However, the functional relevance of the miRNA editome is largely unknown in Parkinson’s disease (PD). By analyzing small RNA sequencing profiles of brain tissues of 43 PD patients and 88 normal controls, we found that the editing levels of five A-to-I and two C-to-U editing sites are significantly correlated with the ages of normal controls, which is disrupted in PD patients. We totally identified 362 miRNA editing sites with significantly different editing levels in prefrontal cortices of PD patients (PD-PC) compared to results of normal controls. We experimentally validated that A-to-I edited miR-497-5p, with significantly higher expression levels in PD-PC compared to normal controls, directly represses OPA1 and VAPB. Furthermore, overexpression of A-to-I edited miR-497-5p downregulates OPA1 and VAPB in two cell lines, and inhibits proliferation of glioma cells. These results suggest that the hyperediting of miR-497-5p in PD contributes to enhanced progressive neurodegeneration of PD patients. Our results provide new insights into the mechanistic understanding, novel diagnostics, and therapeutic clues of PD.https://www.mdpi.com/2073-4409/12/1/75RNA editingParkinson’s diseasehsa-miR-497-5pOPA1VAPB |
| spellingShingle | Chenyu Lu Shuchao Ren Wenping Xie Zhigang Zhao Xingwang Wu Shiyong Guo Angbaji Suo Nan Zhou Jun Yang Shuai Wu Yun Zheng Characterizing Relevant MicroRNA Editing Sites in Parkinson’s Disease Cells RNA editing Parkinson’s disease hsa-miR-497-5p OPA1 VAPB |
| title | Characterizing Relevant MicroRNA Editing Sites in Parkinson’s Disease |
| title_full | Characterizing Relevant MicroRNA Editing Sites in Parkinson’s Disease |
| title_fullStr | Characterizing Relevant MicroRNA Editing Sites in Parkinson’s Disease |
| title_full_unstemmed | Characterizing Relevant MicroRNA Editing Sites in Parkinson’s Disease |
| title_short | Characterizing Relevant MicroRNA Editing Sites in Parkinson’s Disease |
| title_sort | characterizing relevant microrna editing sites in parkinson s disease |
| topic | RNA editing Parkinson’s disease hsa-miR-497-5p OPA1 VAPB |
| url | https://www.mdpi.com/2073-4409/12/1/75 |
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