miR-223-3p and miR-24-3p as novel serum-based biomarkers for myotonic dystrophy type 1
Myotonic dystrophy type 1 (DM1) is the most common adult-onset muscular dystrophy, primarily characterized by muscle wasting and weakness. Many biomarkers already exist in the rapidly developing biomarker research field that aim to improve patients’ care. Limited work, however, has been performed on...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2021-12-01
|
| Series: | Molecular Therapy: Methods & Clinical Development |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2329050121001443 |
| _version_ | 1818388822893789184 |
|---|---|
| author | Demetris Koutalianos Andrie Koutsoulidou Chrystalla Mytidou Andrea C. Kakouri Anastasis Oulas Marios Tomazou Tassos C. Kyriakides Marianna Prokopi Konstantinos Kapnisis Nikoletta Nikolenko Chris Turner Anna Lusakowska Katarzyna Janiszewska George K. Papadimas Constantinos Papadopoulos Evangelia Kararizou George M. Spyrou Geneviève Gourdon Eleni Zamba Papanicolaou Grainne Gorman Andreas Anayiotos Hanns Lochmüller Leonidas A. Phylactou |
| author_facet | Demetris Koutalianos Andrie Koutsoulidou Chrystalla Mytidou Andrea C. Kakouri Anastasis Oulas Marios Tomazou Tassos C. Kyriakides Marianna Prokopi Konstantinos Kapnisis Nikoletta Nikolenko Chris Turner Anna Lusakowska Katarzyna Janiszewska George K. Papadimas Constantinos Papadopoulos Evangelia Kararizou George M. Spyrou Geneviève Gourdon Eleni Zamba Papanicolaou Grainne Gorman Andreas Anayiotos Hanns Lochmüller Leonidas A. Phylactou |
| author_sort | Demetris Koutalianos |
| collection | DOAJ |
| description | Myotonic dystrophy type 1 (DM1) is the most common adult-onset muscular dystrophy, primarily characterized by muscle wasting and weakness. Many biomarkers already exist in the rapidly developing biomarker research field that aim to improve patients’ care. Limited work, however, has been performed on rare diseases, including DM1. We have previously shown that specific microRNAs (miRNAs) can be used as potential biomarkers for DM1 progression. In this report, we aimed to identify novel serum-based biomarkers for DM1 through high-throughput next-generation sequencing. A number of miRNAs were identified that are able to distinguish DM1 patients from healthy individuals. Two miRNAs were selected, and their association with the disease was validated in a larger panel of patients. Further investigation of miR-223-3p, miR-24-3p, and the four previously identified miRNAs, miR-1-3p, miR-133a-3p, miR-133b-3p, and miR-206-3p, showed elevated levels in a DM1 mouse model for all six miRNAs circulating in the serum compared to healthy controls. Importantly, the levels of miR-223-3p, but not the other five miRNAs, were found to be significantly downregulated in five skeletal muscles and heart tissues of DM1 mice compared to controls. This result provides significant evidence for its involvement in disease manifestation. |
| first_indexed | 2024-12-14T04:31:57Z |
| format | Article |
| id | doaj.art-0df8908873d4446eb6c45e3b522382e8 |
| institution | Directory Open Access Journal |
| issn | 2329-0501 |
| language | English |
| last_indexed | 2024-12-14T04:31:57Z |
| publishDate | 2021-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Methods & Clinical Development |
| spelling | doaj.art-0df8908873d4446eb6c45e3b522382e82022-12-21T23:17:04ZengElsevierMolecular Therapy: Methods & Clinical Development2329-05012021-12-0123169183miR-223-3p and miR-24-3p as novel serum-based biomarkers for myotonic dystrophy type 1Demetris Koutalianos0Andrie Koutsoulidou1Chrystalla Mytidou2Andrea C. Kakouri3Anastasis Oulas4Marios Tomazou5Tassos C. Kyriakides6Marianna Prokopi7Konstantinos Kapnisis8Nikoletta Nikolenko9Chris Turner10Anna Lusakowska11Katarzyna Janiszewska12George K. Papadimas13Constantinos Papadopoulos14Evangelia Kararizou15George M. Spyrou16Geneviève Gourdon17Eleni Zamba Papanicolaou18Grainne Gorman19Andreas Anayiotos20Hanns Lochmüller21Leonidas A. Phylactou22Department of Molecular Genetics, Function and Therapy, The Cyprus Institute of Neurology and Genetics, 6 Iroon Avenue, 2371 Ayios Dometios, Nicosia, Cyprus, PO Box 23462, 1683 Nicosia, CyprusDepartment of Molecular Genetics, Function and Therapy, The Cyprus Institute of Neurology and Genetics, 6 Iroon Avenue, 2371 Ayios Dometios, Nicosia, Cyprus, PO Box 23462, 1683 Nicosia, Cyprus; The Cyprus School of Molecular Medicine, The Cyprus Institute of Neurology and Genetics, 6 Iroon Avenue, 2371 Ayios Dometios, Nicosia, Cyprus, PO Box 23462, 1683 Nicosia, CyprusDepartment of Molecular Genetics, Function and Therapy, The Cyprus Institute of Neurology and Genetics, 6 Iroon Avenue, 2371 Ayios Dometios, Nicosia, Cyprus, PO Box 23462, 1683 Nicosia, Cyprus; The Cyprus School of Molecular Medicine, The Cyprus Institute of Neurology and Genetics, 6 Iroon Avenue, 2371 Ayios Dometios, Nicosia, Cyprus, PO Box 23462, 1683 Nicosia, CyprusThe Cyprus School of Molecular Medicine, The Cyprus Institute of Neurology and Genetics, 6 Iroon Avenue, 2371 Ayios Dometios, Nicosia, Cyprus, PO Box 23462, 1683 Nicosia, Cyprus; Department of Bioinformatics, The Cyprus Institute of Neurology and Genetics, 6 Iroon Avenue, 2371 Ayios Dometios, Nicosia, Cyprus, PO Box 23462, 1683 Nicosia, Cyprus; Department of Neurogenetics, The Cyprus Institute of Neurology and Genetics, 6 Iroon Avenue, 2371 Ayios Dometios, Nicosia, Cyprus, PO Box 23462, 1683 Nicosia, CyprusThe Cyprus School of Molecular Medicine, The Cyprus Institute of Neurology and Genetics, 6 Iroon Avenue, 2371 Ayios Dometios, Nicosia, Cyprus, PO Box 23462, 1683 Nicosia, Cyprus; Department of Bioinformatics, The Cyprus Institute of Neurology and Genetics, 6 Iroon Avenue, 2371 Ayios Dometios, Nicosia, Cyprus, PO Box 23462, 1683 Nicosia, CyprusThe Cyprus School of Molecular Medicine, The Cyprus Institute of Neurology and Genetics, 6 Iroon Avenue, 2371 Ayios Dometios, Nicosia, Cyprus, PO Box 23462, 1683 Nicosia, Cyprus; Department of Bioinformatics, The Cyprus Institute of Neurology and Genetics, 6 Iroon Avenue, 2371 Ayios Dometios, Nicosia, Cyprus, PO Box 23462, 1683 Nicosia, Cyprus; Department of Neurogenetics, The Cyprus Institute of Neurology and Genetics, 6 Iroon Avenue, 2371 Ayios Dometios, Nicosia, Cyprus, PO Box 23462, 1683 Nicosia, CyprusYale Center for Analytical Sciences, Yale School of Public Health, 300 George Street, Suite 555, New Haven, CT 06520, USADepartment of Mechanical Engineering and Materials Science and Engineering, Cyprus University of Technology, 45 Kitiou Kyprianou Str., 3041 Limassol, Cyprus; Theramir Ltd, 13 Georgiou Karaiskaki Str., 3032 Limassol, CyprusDepartment of Mechanical Engineering and Materials Science and Engineering, Cyprus University of Technology, 45 Kitiou Kyprianou Str., 3041 Limassol, CyprusNational Hospital for Neurology and Neurosurgery, Queen Square, University College London Hospitals NHS Foundation Trust, London, UKNational Hospital for Neurology and Neurosurgery, Queen Square, University College London Hospitals NHS Foundation Trust, London, UKDepartment of Neurology, Medical University of Warsaw, Warsaw, PolandDepartment of Neurology, Central Hospital of Medical University of Warsaw, Warsaw, PolandDepartment of Neurology, Eginitio Hospital, Medical School of Athens, 74 Vasilissis Sofias, 11528 Athens, GreeceDepartment of Neurology, Eginitio Hospital, Medical School of Athens, 74 Vasilissis Sofias, 11528 Athens, GreeceDepartment of Neurology, Eginitio Hospital, Medical School of Athens, 74 Vasilissis Sofias, 11528 Athens, GreeceThe Cyprus School of Molecular Medicine, The Cyprus Institute of Neurology and Genetics, 6 Iroon Avenue, 2371 Ayios Dometios, Nicosia, Cyprus, PO Box 23462, 1683 Nicosia, Cyprus; Department of Bioinformatics, The Cyprus Institute of Neurology and Genetics, 6 Iroon Avenue, 2371 Ayios Dometios, Nicosia, Cyprus, PO Box 23462, 1683 Nicosia, CyprusInserm, Sorbonne University, Institute of Myology, Center of Research in Myology, Paris, FranceThe Cyprus School of Molecular Medicine, The Cyprus Institute of Neurology and Genetics, 6 Iroon Avenue, 2371 Ayios Dometios, Nicosia, Cyprus, PO Box 23462, 1683 Nicosia, Cyprus; Neurology Clinic D, The Cyprus Institute of Neurology and Genetics, 6 Iroon Avenue, 2371 Ayios Dometios, Nicosia, Cyprus, PO Box 23462, 1683 Nicosia, CyprusWellcome Trust Centre for Mitochondrial Research, Institute of Neuroscience, University of Newcastle, Newcastle, UKDepartment of Mechanical Engineering and Materials Science and Engineering, Cyprus University of Technology, 45 Kitiou Kyprianou Str., 3041 Limassol, CyprusDepartment of Neuropediatrics and Muscle Disorders, Medical Centre–University of Freiburg, Faculty of Medicine, Freiburg, Germany; Children’s Hospital of Eastern Ontario Research Institute, Division of Neurology, Department of Medicine, The Ottawa Hospital, and Brain and Mind Research Institute, University of Ottawa, Ottawa, CanadaDepartment of Molecular Genetics, Function and Therapy, The Cyprus Institute of Neurology and Genetics, 6 Iroon Avenue, 2371 Ayios Dometios, Nicosia, Cyprus, PO Box 23462, 1683 Nicosia, Cyprus; The Cyprus School of Molecular Medicine, The Cyprus Institute of Neurology and Genetics, 6 Iroon Avenue, 2371 Ayios Dometios, Nicosia, Cyprus, PO Box 23462, 1683 Nicosia, Cyprus; Corresponding author: Leonidas A. Phylactou, Department of Molecular Genetics, Function and Therapy, The Cyprus Institute of Neurology and Genetics, 6 Iroon Avenue, 2371 Ayios Dometios, Nicosia, Cyprus, PO Box 23462, 1683 Nicosia, Cyprus.Myotonic dystrophy type 1 (DM1) is the most common adult-onset muscular dystrophy, primarily characterized by muscle wasting and weakness. Many biomarkers already exist in the rapidly developing biomarker research field that aim to improve patients’ care. Limited work, however, has been performed on rare diseases, including DM1. We have previously shown that specific microRNAs (miRNAs) can be used as potential biomarkers for DM1 progression. In this report, we aimed to identify novel serum-based biomarkers for DM1 through high-throughput next-generation sequencing. A number of miRNAs were identified that are able to distinguish DM1 patients from healthy individuals. Two miRNAs were selected, and their association with the disease was validated in a larger panel of patients. Further investigation of miR-223-3p, miR-24-3p, and the four previously identified miRNAs, miR-1-3p, miR-133a-3p, miR-133b-3p, and miR-206-3p, showed elevated levels in a DM1 mouse model for all six miRNAs circulating in the serum compared to healthy controls. Importantly, the levels of miR-223-3p, but not the other five miRNAs, were found to be significantly downregulated in five skeletal muscles and heart tissues of DM1 mice compared to controls. This result provides significant evidence for its involvement in disease manifestation.http://www.sciencedirect.com/science/article/pii/S2329050121001443miRNAsmyotonic dystrophybiomarkerssmall extracellular vesiclesmuscleheart |
| spellingShingle | Demetris Koutalianos Andrie Koutsoulidou Chrystalla Mytidou Andrea C. Kakouri Anastasis Oulas Marios Tomazou Tassos C. Kyriakides Marianna Prokopi Konstantinos Kapnisis Nikoletta Nikolenko Chris Turner Anna Lusakowska Katarzyna Janiszewska George K. Papadimas Constantinos Papadopoulos Evangelia Kararizou George M. Spyrou Geneviève Gourdon Eleni Zamba Papanicolaou Grainne Gorman Andreas Anayiotos Hanns Lochmüller Leonidas A. Phylactou miR-223-3p and miR-24-3p as novel serum-based biomarkers for myotonic dystrophy type 1 Molecular Therapy: Methods & Clinical Development miRNAs myotonic dystrophy biomarkers small extracellular vesicles muscle heart |
| title | miR-223-3p and miR-24-3p as novel serum-based biomarkers for myotonic dystrophy type 1 |
| title_full | miR-223-3p and miR-24-3p as novel serum-based biomarkers for myotonic dystrophy type 1 |
| title_fullStr | miR-223-3p and miR-24-3p as novel serum-based biomarkers for myotonic dystrophy type 1 |
| title_full_unstemmed | miR-223-3p and miR-24-3p as novel serum-based biomarkers for myotonic dystrophy type 1 |
| title_short | miR-223-3p and miR-24-3p as novel serum-based biomarkers for myotonic dystrophy type 1 |
| title_sort | mir 223 3p and mir 24 3p as novel serum based biomarkers for myotonic dystrophy type 1 |
| topic | miRNAs myotonic dystrophy biomarkers small extracellular vesicles muscle heart |
| url | http://www.sciencedirect.com/science/article/pii/S2329050121001443 |
| work_keys_str_mv | AT demetriskoutalianos mir2233pandmir243pasnovelserumbasedbiomarkersformyotonicdystrophytype1 AT andriekoutsoulidou mir2233pandmir243pasnovelserumbasedbiomarkersformyotonicdystrophytype1 AT chrystallamytidou mir2233pandmir243pasnovelserumbasedbiomarkersformyotonicdystrophytype1 AT andreackakouri mir2233pandmir243pasnovelserumbasedbiomarkersformyotonicdystrophytype1 AT anastasisoulas mir2233pandmir243pasnovelserumbasedbiomarkersformyotonicdystrophytype1 AT mariostomazou mir2233pandmir243pasnovelserumbasedbiomarkersformyotonicdystrophytype1 AT tassosckyriakides mir2233pandmir243pasnovelserumbasedbiomarkersformyotonicdystrophytype1 AT mariannaprokopi mir2233pandmir243pasnovelserumbasedbiomarkersformyotonicdystrophytype1 AT konstantinoskapnisis mir2233pandmir243pasnovelserumbasedbiomarkersformyotonicdystrophytype1 AT nikolettanikolenko mir2233pandmir243pasnovelserumbasedbiomarkersformyotonicdystrophytype1 AT christurner mir2233pandmir243pasnovelserumbasedbiomarkersformyotonicdystrophytype1 AT annalusakowska mir2233pandmir243pasnovelserumbasedbiomarkersformyotonicdystrophytype1 AT katarzynajaniszewska mir2233pandmir243pasnovelserumbasedbiomarkersformyotonicdystrophytype1 AT georgekpapadimas mir2233pandmir243pasnovelserumbasedbiomarkersformyotonicdystrophytype1 AT constantinospapadopoulos mir2233pandmir243pasnovelserumbasedbiomarkersformyotonicdystrophytype1 AT evangeliakararizou mir2233pandmir243pasnovelserumbasedbiomarkersformyotonicdystrophytype1 AT georgemspyrou mir2233pandmir243pasnovelserumbasedbiomarkersformyotonicdystrophytype1 AT genevievegourdon mir2233pandmir243pasnovelserumbasedbiomarkersformyotonicdystrophytype1 AT elenizambapapanicolaou mir2233pandmir243pasnovelserumbasedbiomarkersformyotonicdystrophytype1 AT grainnegorman mir2233pandmir243pasnovelserumbasedbiomarkersformyotonicdystrophytype1 AT andreasanayiotos mir2233pandmir243pasnovelserumbasedbiomarkersformyotonicdystrophytype1 AT hannslochmuller mir2233pandmir243pasnovelserumbasedbiomarkersformyotonicdystrophytype1 AT leonidasaphylactou mir2233pandmir243pasnovelserumbasedbiomarkersformyotonicdystrophytype1 |