Circulating Non-Coding RNA Levels Are Altered in Autosomal Dominant Frontotemporal Dementia
Frontotemporal Dementia (FTD) represents a highly heritable neurodegenerative disorder. Most of the heritability is caused by autosomal dominant mutations in the Microtubule-Associated Protein Tau (<i>MAPT</i>), Progranulin (<i>GRN</i>), and the pathologic exanucleotide expan...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-11-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/23/14723 |
| _version_ | 1797463168498270208 |
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| author | Chiara Fenoglio Maria Serpente Caterina Visconte Marina Arcaro Federica Sorrentino Marianna D’Anca Andrea Arighi Emanuela Rotondo Roberto Vimercati Giacomina Rossi Elio Scarpini Daniela Galimberti |
| author_facet | Chiara Fenoglio Maria Serpente Caterina Visconte Marina Arcaro Federica Sorrentino Marianna D’Anca Andrea Arighi Emanuela Rotondo Roberto Vimercati Giacomina Rossi Elio Scarpini Daniela Galimberti |
| author_sort | Chiara Fenoglio |
| collection | DOAJ |
| description | Frontotemporal Dementia (FTD) represents a highly heritable neurodegenerative disorder. Most of the heritability is caused by autosomal dominant mutations in the Microtubule-Associated Protein Tau (<i>MAPT</i>), Progranulin (<i>GRN</i>), and the pathologic exanucleotide expansion of <i>C9ORF72</i> genes. At the pathological level, either the tau or the TAR DNA-binding protein (TDP-43) account for almost all cases of FTD. Pathogenic mechanisms are just arising, and the emerging role of non-coding RNAs (ncRNAs), such as microRNAs (miRNA) and long non-coding RNAs (lncRNAs), have become increasingly evident. Using specific arrays, an exploratory analysis testing the expression levels of 84 miRNAs and 84 lncRNAs has been performed in a population consisting of 24 genetic FTD patients (eight <i>GRN</i>, eight <i>C9ORF72</i>, and eight <i>MAPT</i> mutation carriers), eight sporadic FTD patients, and eight healthy controls. The results showed a generalized ncRNA downregulation in patients carrying <i>GRN</i> and <i>C9ORF72</i> when compared with the controls, with statistically significant results for the following miRNAs: miR-155-5p (Fold Change FC: 0.45, <i>p</i> = 0.037 FDR = 0.52), miR-15a-5p (FC: 0.13, <i>p</i> = 0.027, FDR = 1), miR-222-3p (FC: 0.13, <i>p</i> = 0.027, FDR = 0.778), miR-140-3p (FC: 0.096, <i>p</i> = 0.034, FRD = 0.593), miR-106b-5p (FC: 0.13, <i>p</i> = 0.02, FDR = 0.584) and an upregulation solely for miR-124-3p (FC: 2.1, <i>p</i> = 0.01, FDR = 0.893). Conversely, <i>MAPT</i> mutation carriers showed a generalized robust upregulation in several ncRNAs, specifically for miR-222-3p (FC: 22.3, <i>p</i> = 7 × 10<sup>−6</sup>, FDR = 0.117), miR-15a-5p (FC: 30.2, <i>p</i> = 0.008, FDR = 0.145), miR-27a-3p (FC: 27.8, <i>p</i> = 6 × 10<sup>−6</sup>, FDR = 0.0005), miR-223-3p (FC: 18.9, <i>p</i> = 0.005, FDR = 0.117), and miR-16-5p (FC: 10.9, <i>p</i> = 5.26 × 10<sup>−5</sup>, FDR = 0.001). These results suggest a clear, distinctive pattern of dysregulation among ncRNAs and specific enrichment gene pathways between mutations associated with the TDP-43 and tau pathologies. Nevertheless, these preliminary results need to be confirmed in a larger independent cohort. |
| first_indexed | 2024-03-09T17:46:50Z |
| format | Article |
| id | doaj.art-cc09a4a70ac745988524ecab2df2f497 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T17:46:50Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-cc09a4a70ac745988524ecab2df2f4972023-11-24T11:06:46ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-11-0123231472310.3390/ijms232314723Circulating Non-Coding RNA Levels Are Altered in Autosomal Dominant Frontotemporal DementiaChiara Fenoglio0Maria Serpente1Caterina Visconte2Marina Arcaro3Federica Sorrentino4Marianna D’Anca5Andrea Arighi6Emanuela Rotondo7Roberto Vimercati8Giacomina Rossi9Elio Scarpini10Daniela Galimberti11Department of Pathophysiology and Transplantation, Dino Ferrari Center, University of Milan, 20122 Milan, ItalyFondazione, IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, 20122 Milan, ItalyDepartment of Biomedical, Surgical and Dental Sciences, Dino Ferrari Center, University of Milan, 20122 Milan, ItalyFondazione, IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, 20122 Milan, ItalyDepartment of Biomedical, Surgical and Dental Sciences, Dino Ferrari Center, University of Milan, 20122 Milan, ItalyFondazione, IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, 20122 Milan, ItalyFondazione, IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, 20122 Milan, ItalyFondazione, IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, 20122 Milan, ItalyFondazione, IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, 20122 Milan, ItalyUnit of Neurology V—Neuropathology, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20133 Milan, ItalyFondazione, IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, 20122 Milan, ItalyFondazione, IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, 20122 Milan, ItalyFrontotemporal Dementia (FTD) represents a highly heritable neurodegenerative disorder. Most of the heritability is caused by autosomal dominant mutations in the Microtubule-Associated Protein Tau (<i>MAPT</i>), Progranulin (<i>GRN</i>), and the pathologic exanucleotide expansion of <i>C9ORF72</i> genes. At the pathological level, either the tau or the TAR DNA-binding protein (TDP-43) account for almost all cases of FTD. Pathogenic mechanisms are just arising, and the emerging role of non-coding RNAs (ncRNAs), such as microRNAs (miRNA) and long non-coding RNAs (lncRNAs), have become increasingly evident. Using specific arrays, an exploratory analysis testing the expression levels of 84 miRNAs and 84 lncRNAs has been performed in a population consisting of 24 genetic FTD patients (eight <i>GRN</i>, eight <i>C9ORF72</i>, and eight <i>MAPT</i> mutation carriers), eight sporadic FTD patients, and eight healthy controls. The results showed a generalized ncRNA downregulation in patients carrying <i>GRN</i> and <i>C9ORF72</i> when compared with the controls, with statistically significant results for the following miRNAs: miR-155-5p (Fold Change FC: 0.45, <i>p</i> = 0.037 FDR = 0.52), miR-15a-5p (FC: 0.13, <i>p</i> = 0.027, FDR = 1), miR-222-3p (FC: 0.13, <i>p</i> = 0.027, FDR = 0.778), miR-140-3p (FC: 0.096, <i>p</i> = 0.034, FRD = 0.593), miR-106b-5p (FC: 0.13, <i>p</i> = 0.02, FDR = 0.584) and an upregulation solely for miR-124-3p (FC: 2.1, <i>p</i> = 0.01, FDR = 0.893). Conversely, <i>MAPT</i> mutation carriers showed a generalized robust upregulation in several ncRNAs, specifically for miR-222-3p (FC: 22.3, <i>p</i> = 7 × 10<sup>−6</sup>, FDR = 0.117), miR-15a-5p (FC: 30.2, <i>p</i> = 0.008, FDR = 0.145), miR-27a-3p (FC: 27.8, <i>p</i> = 6 × 10<sup>−6</sup>, FDR = 0.0005), miR-223-3p (FC: 18.9, <i>p</i> = 0.005, FDR = 0.117), and miR-16-5p (FC: 10.9, <i>p</i> = 5.26 × 10<sup>−5</sup>, FDR = 0.001). These results suggest a clear, distinctive pattern of dysregulation among ncRNAs and specific enrichment gene pathways between mutations associated with the TDP-43 and tau pathologies. Nevertheless, these preliminary results need to be confirmed in a larger independent cohort.https://www.mdpi.com/1422-0067/23/23/14723frontotemporal diseasemicroRNAlong non-coding RNA<i>GRN</i><i>MAPT</i><i>C9ORF72</i> |
| spellingShingle | Chiara Fenoglio Maria Serpente Caterina Visconte Marina Arcaro Federica Sorrentino Marianna D’Anca Andrea Arighi Emanuela Rotondo Roberto Vimercati Giacomina Rossi Elio Scarpini Daniela Galimberti Circulating Non-Coding RNA Levels Are Altered in Autosomal Dominant Frontotemporal Dementia International Journal of Molecular Sciences frontotemporal disease microRNA long non-coding RNA <i>GRN</i> <i>MAPT</i> <i>C9ORF72</i> |
| title | Circulating Non-Coding RNA Levels Are Altered in Autosomal Dominant Frontotemporal Dementia |
| title_full | Circulating Non-Coding RNA Levels Are Altered in Autosomal Dominant Frontotemporal Dementia |
| title_fullStr | Circulating Non-Coding RNA Levels Are Altered in Autosomal Dominant Frontotemporal Dementia |
| title_full_unstemmed | Circulating Non-Coding RNA Levels Are Altered in Autosomal Dominant Frontotemporal Dementia |
| title_short | Circulating Non-Coding RNA Levels Are Altered in Autosomal Dominant Frontotemporal Dementia |
| title_sort | circulating non coding rna levels are altered in autosomal dominant frontotemporal dementia |
| topic | frontotemporal disease microRNA long non-coding RNA <i>GRN</i> <i>MAPT</i> <i>C9ORF72</i> |
| url | https://www.mdpi.com/1422-0067/23/23/14723 |
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