Therapeutic effects of miR-937-3p by targeting NTN1 expression and regulating apoptosis in an Aβ-induced neuronal cell death
Abstract MicroRNAs (miRNAs) have multiple functions that regulate gene expression in various species. Few studies have explored the effects of miRNAs on the pathogenesis of Alzheimer’s disease (AD); however, the potential neuroprotective effects of miRNAs on AD, particularly by targeting neuronal ma...
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Nature Portfolio
2025-07-01
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| Online Access: | https://doi.org/10.1038/s41598-025-08015-0 |
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| author | Jiyun Choi Haewon Jeong Mahesh Ramalingam Jinsu Hwang Seong-Jin Kim Byeong C. Kim Han-Seong Jeong Sujeong Jang |
| author_facet | Jiyun Choi Haewon Jeong Mahesh Ramalingam Jinsu Hwang Seong-Jin Kim Byeong C. Kim Han-Seong Jeong Sujeong Jang |
| author_sort | Jiyun Choi |
| collection | DOAJ |
| description | Abstract MicroRNAs (miRNAs) have multiple functions that regulate gene expression in various species. Few studies have explored the effects of miRNAs on the pathogenesis of Alzheimer’s disease (AD); however, the potential neuroprotective effects of miRNAs on AD, particularly by targeting neuronal markers, remain unclear. In this study, we suggested potential neuroprotective roles for miR-937-3p in an in vitro AD model, which has not been extensively studied. Our biological analysis confirmed that miR-937-3p participated in neuronal protection and differentiation. We selected miR-937-3p as a novel candidate and identified Netrin1 (NTN1), an axon guidance regulator, as its target gene via qPCR analysis and luciferase assay. Additionally, FACS analysis revealed a reduction in apoptosis levels in Aβ-treated cells following treatment with the miR-937-3p-I. Western blot analysis showed that the expression of Mcl-1, an anti-apoptotic marker, increased with miR-937-3p-I treatment in an in vitro AD model. Interestingly, the levels of pro-caspase 7, pro-caspase 3, and pro-PARP, which are usually downregulated when their cleaved forms are upregulated, were found to increase with miR-937-3p-I treatment. The expression levels of neuronal markers such as NeuN, NFH, Tuj1, SYP, and MAP2 were enhanced by miR-937-3p-I treatment in the in vitro AD model. Therefore, miR-937-3p inhibition might play a therapeutic and neuroprotective role in AD by promoting NTN1 expression and repressing the apoptotic pathway. |
| format | Article |
| id | doaj-art-41afd07ead114696aedf49f02eef8767 |
| institution | DOAJ |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-41afd07ead114696aedf49f02eef87672025-08-20T03:03:33ZengNature PortfolioScientific Reports2045-23222025-07-0115111510.1038/s41598-025-08015-0Therapeutic effects of miR-937-3p by targeting NTN1 expression and regulating apoptosis in an Aβ-induced neuronal cell deathJiyun Choi0Haewon Jeong1Mahesh Ramalingam2Jinsu Hwang3Seong-Jin Kim4Byeong C. Kim5Han-Seong Jeong6Sujeong Jang7Department of Physiology, Chonnam National University Medical SchoolDepartment of Physiology, Chonnam National University Medical SchoolDepartment of Physiology, Chonnam National University Medical SchoolDepartment of Physiology, Chonnam National University Medical SchoolDepartment of Dermatology, Chonnam National University Hospital, Chonnam National University Medical SchoolDepartment of Neurology, Chonnam National University Hospital, Chonnam National University Medical SchoolDepartment of Physiology, Chonnam National University Medical SchoolDepartment of Physiology, Chonnam National University Medical SchoolAbstract MicroRNAs (miRNAs) have multiple functions that regulate gene expression in various species. Few studies have explored the effects of miRNAs on the pathogenesis of Alzheimer’s disease (AD); however, the potential neuroprotective effects of miRNAs on AD, particularly by targeting neuronal markers, remain unclear. In this study, we suggested potential neuroprotective roles for miR-937-3p in an in vitro AD model, which has not been extensively studied. Our biological analysis confirmed that miR-937-3p participated in neuronal protection and differentiation. We selected miR-937-3p as a novel candidate and identified Netrin1 (NTN1), an axon guidance regulator, as its target gene via qPCR analysis and luciferase assay. Additionally, FACS analysis revealed a reduction in apoptosis levels in Aβ-treated cells following treatment with the miR-937-3p-I. Western blot analysis showed that the expression of Mcl-1, an anti-apoptotic marker, increased with miR-937-3p-I treatment in an in vitro AD model. Interestingly, the levels of pro-caspase 7, pro-caspase 3, and pro-PARP, which are usually downregulated when their cleaved forms are upregulated, were found to increase with miR-937-3p-I treatment. The expression levels of neuronal markers such as NeuN, NFH, Tuj1, SYP, and MAP2 were enhanced by miR-937-3p-I treatment in the in vitro AD model. Therefore, miR-937-3p inhibition might play a therapeutic and neuroprotective role in AD by promoting NTN1 expression and repressing the apoptotic pathway.https://doi.org/10.1038/s41598-025-08015-0MiRNAADNTN1ApoptosisNeuroprotection |
| spellingShingle | Jiyun Choi Haewon Jeong Mahesh Ramalingam Jinsu Hwang Seong-Jin Kim Byeong C. Kim Han-Seong Jeong Sujeong Jang Therapeutic effects of miR-937-3p by targeting NTN1 expression and regulating apoptosis in an Aβ-induced neuronal cell death Scientific Reports MiRNA AD NTN1 Apoptosis Neuroprotection |
| title | Therapeutic effects of miR-937-3p by targeting NTN1 expression and regulating apoptosis in an Aβ-induced neuronal cell death |
| title_full | Therapeutic effects of miR-937-3p by targeting NTN1 expression and regulating apoptosis in an Aβ-induced neuronal cell death |
| title_fullStr | Therapeutic effects of miR-937-3p by targeting NTN1 expression and regulating apoptosis in an Aβ-induced neuronal cell death |
| title_full_unstemmed | Therapeutic effects of miR-937-3p by targeting NTN1 expression and regulating apoptosis in an Aβ-induced neuronal cell death |
| title_short | Therapeutic effects of miR-937-3p by targeting NTN1 expression and regulating apoptosis in an Aβ-induced neuronal cell death |
| title_sort | therapeutic effects of mir 937 3p by targeting ntn1 expression and regulating apoptosis in an aβ induced neuronal cell death |
| topic | MiRNA AD NTN1 Apoptosis Neuroprotection |
| url | https://doi.org/10.1038/s41598-025-08015-0 |
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