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Downregulated miR-18b-5p triggers apoptosis by inhibition of calcium signaling and neuronal cell differentiation in transgenic SOD1 (G93A) mice and SOD1 (G17S and G86S) ALS patients
DC Field | Value | Language |
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dc.contributor.author | Kim, Ki Y | - |
dc.contributor.author | Kim, Yu R | - |
dc.contributor.author | Choi, Kyung W | - |
dc.contributor.author | Lee, Mijung | - |
dc.contributor.author | Lee, Somyung | - |
dc.contributor.author | Im, Wooseok | - |
dc.contributor.author | Shin, Je-Young | - |
dc.contributor.author | Kim, Jin Y | - |
dc.contributor.author | Hong, Yoon H | - |
dc.contributor.author | Kim, Manho | - |
dc.contributor.author | Kim, Jong-Il | - |
dc.contributor.author | Sung, Jung-Joon | - |
dc.date.accessioned | 2020-09-09T05:26:45Z | - |
dc.date.available | 2020-09-09T05:26:45Z | - |
dc.date.issued | 2020-07-01 | - |
dc.identifier.citation | Translational Neurodegeneration. 2020 Jul 01;9(1):23 | - |
dc.identifier.uri | https://doi.org/10.1186/s40035-020-00203-4 | - |
dc.identifier.uri | https://hdl.handle.net/10371/168838 | - |
dc.description.abstract | Abstract
Background MicroRNAs (miRNAs) are endogenous non-coding RNAs that regulate gene expression at the post-transcriptional level and are key modulators in neurodegenerative diseases. Overexpressed miRNAs play an important role in ALS; however, the pathogenic mechanisms of deregulated miRNAs are still unclear. Methods We aimed to assess the dysfunction of RNAs or miRNAs in fALS (SOD1 mutations). We compared the RNA-seq of subcellular fractions in NSC-34 WT (hSOD1) and MT (hSOD1 (G93A)) cells to find altered RNAs or miRNAs. We identified that Hif1α and Mef2c were upregulated, and Mctp1 and Rarb were downregulated in the cytoplasm of NSC-34 MT cells. Results SOD1 mutations decreased the level of miR-18b-5p. Induced Hif1α which is the target for miR-18b increased Mef2c expression as a transcription factor. Mef2c upregulated miR-206 as a transcription factor. Inhibition of Mctp1 and Rarb which are targets of miR-206 induces intracellular Ca2+ levels and reduces cell differentiation, respectively. We confirmed that miR-18b-5p pathway was also observed in G93A Tg, fALS (G86S) patient, and iPSC-derived motor neurons from fALS (G17S) patient. Conclusions Our data indicate that SOD1 mutation decreases miR-18b-5p, which sequentially regulates Hif1α, Mef2c, miR-206, Mctp1 and Rarb in fALS-linked SOD1 mutation. These results provide new insights into the downregulation of miR-18b-5p dependent pathogenic mechanisms of ALS. | - |
dc.title | Downregulated miR-18b-5p triggers apoptosis by inhibition of calcium signaling and neuronal cell differentiation in transgenic SOD1 (G93A) mice and SOD1 (G17S and G86S) ALS patients | - |
dc.type | Journal Article | - |
dc.language.rfc3066 | en | - |
dc.rights.holder | The Author(s) | - |
dc.date.updated | 2020-07-05T04:02:40Z | - |
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