Circulating microRNAs in patients with immune thrombocytopenia before and after treatment with thrombopoietin-receptor agonists
MicroRNAs (miRNAs) are small non-coding RNAs involved in the regulation of gene expression. Dysregulated expression of several miRNAs has been found in primary immune thrombocytopenia (ITP) suggesting that miRNAs are likely involved in the pathogenesis of ITP. We aimed to explore the differential ex...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2020-02-01
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| Series: | Platelets |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/09537104.2019.1585527 |
| _version_ | 1797684216792612864 |
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| author | Lamya Garabet Waleed Ghanima Anbjørg Rangberg Raul Teruel-Montoya Constantino Martinez Maria Luisa Lozano Camilla F. Nystrand James B. Bussel Per Morten Sandset Christine M. Jonassen |
| author_facet | Lamya Garabet Waleed Ghanima Anbjørg Rangberg Raul Teruel-Montoya Constantino Martinez Maria Luisa Lozano Camilla F. Nystrand James B. Bussel Per Morten Sandset Christine M. Jonassen |
| author_sort | Lamya Garabet |
| collection | DOAJ |
| description | MicroRNAs (miRNAs) are small non-coding RNAs involved in the regulation of gene expression. Dysregulated expression of several miRNAs has been found in primary immune thrombocytopenia (ITP) suggesting that miRNAs are likely involved in the pathogenesis of ITP. We aimed to explore the differential expression of miRNAs in patients with ITP before and after starting treatment with thrombopoietin-receptor agonists (TPO-RAs) to clarify their roles in the pathophysiology of ITP, and as potential diagnostic and prognostic markers of this disorder. We performed a profiling study where 179 miRNAs were analyzed in eight ITP patients before and during treatment with TPO-RAs and in eight controls using miRNA PCR panel; 81 miRNAs were differentially expressed in ITP patients compared to controls, and 14 miRNAs showed significant changes during TPO-RA-treatment. Ten miRNAs were selected for validation that was performed in 23 patients and 22 controls using droplet digital PCR. Three miRNAs were found to be differentially expressed in ITP patients before TPO-RA-treatment compared to controls: miR-199a-5p was down-regulated (p = 0.0001), miR-33a-5p (p = 0.0002) and miR-195-5p (p = 0.035) were up-regulated. Treatment with TPO-RAs resulted in changes in six miRNAs including miR-199a-5p (p = 0.001), miR-33a-5p (p = 0.003), miR-382-5p (p = 0.004), miR-92b-3p (p = 0.005), miR-26a-5p (p = 0.008) and miR-221-3p (p = 0.023); while miR-195-5p remained unchanged and significantly higher than in controls, despite the increase in the platelet count, which may indicate its possible role in the pathophysiology of ITP. Regression analysis revealed that pre-treatment levels of miR-199a-5p and miR-221-3p could help to predict platelet response to TPO-RA-treatment. ROC curve analysis showed that the combination of miR-199a-5p and miR-33a-5p could distinguish patients with ITP from controls with AUC of 0.93. This study identifies a number of differentially expressed miRNAs in ITP patients before and after initiation of TPO-RAs with potential roles in the pathophysiology, as well as with a possible utility as diagnostic and prognostic biomarkers. These interesting findings deserve further exploration and validation in future studies. |
| first_indexed | 2024-03-12T00:27:14Z |
| format | Article |
| id | doaj.art-a8519fca27444168b9f042182b7e599d |
| institution | Directory Open Access Journal |
| issn | 0953-7104 1369-1635 |
| language | English |
| last_indexed | 2024-03-12T00:27:14Z |
| publishDate | 2020-02-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Platelets |
| spelling | doaj.art-a8519fca27444168b9f042182b7e599d2023-09-15T10:32:01ZengTaylor & Francis GroupPlatelets0953-71041369-16352020-02-0131219820510.1080/09537104.2019.15855271585527Circulating microRNAs in patients with immune thrombocytopenia before and after treatment with thrombopoietin-receptor agonistsLamya Garabet0Waleed Ghanima1Anbjørg Rangberg2Raul Teruel-Montoya3Constantino Martinez4Maria Luisa Lozano5Camilla F. Nystrand6James B. Bussel7Per Morten Sandset8Christine M. Jonassen9Akershus University HospitalUniversity of OsloØstfold Hospital TrustUniversidad de Murcia, IMIB-Arrixaca, Servicio de Hematología y Oncología MédicaUniversidad de Murcia, IMIB-Arrixaca, Servicio de Hematología y Oncología MédicaUniversidad de Murcia, IMIB-Arrixaca, Servicio de Hematología y Oncología MédicaØstfold Hospital TrustNew York Presbyterian Hospital, Weill Cornell MedicineUniversity of OsloØstfold Hospital TrustMicroRNAs (miRNAs) are small non-coding RNAs involved in the regulation of gene expression. Dysregulated expression of several miRNAs has been found in primary immune thrombocytopenia (ITP) suggesting that miRNAs are likely involved in the pathogenesis of ITP. We aimed to explore the differential expression of miRNAs in patients with ITP before and after starting treatment with thrombopoietin-receptor agonists (TPO-RAs) to clarify their roles in the pathophysiology of ITP, and as potential diagnostic and prognostic markers of this disorder. We performed a profiling study where 179 miRNAs were analyzed in eight ITP patients before and during treatment with TPO-RAs and in eight controls using miRNA PCR panel; 81 miRNAs were differentially expressed in ITP patients compared to controls, and 14 miRNAs showed significant changes during TPO-RA-treatment. Ten miRNAs were selected for validation that was performed in 23 patients and 22 controls using droplet digital PCR. Three miRNAs were found to be differentially expressed in ITP patients before TPO-RA-treatment compared to controls: miR-199a-5p was down-regulated (p = 0.0001), miR-33a-5p (p = 0.0002) and miR-195-5p (p = 0.035) were up-regulated. Treatment with TPO-RAs resulted in changes in six miRNAs including miR-199a-5p (p = 0.001), miR-33a-5p (p = 0.003), miR-382-5p (p = 0.004), miR-92b-3p (p = 0.005), miR-26a-5p (p = 0.008) and miR-221-3p (p = 0.023); while miR-195-5p remained unchanged and significantly higher than in controls, despite the increase in the platelet count, which may indicate its possible role in the pathophysiology of ITP. Regression analysis revealed that pre-treatment levels of miR-199a-5p and miR-221-3p could help to predict platelet response to TPO-RA-treatment. ROC curve analysis showed that the combination of miR-199a-5p and miR-33a-5p could distinguish patients with ITP from controls with AUC of 0.93. This study identifies a number of differentially expressed miRNAs in ITP patients before and after initiation of TPO-RAs with potential roles in the pathophysiology, as well as with a possible utility as diagnostic and prognostic biomarkers. These interesting findings deserve further exploration and validation in future studies.http://dx.doi.org/10.1080/09537104.2019.1585527itpmicrornastpo-ras |
| spellingShingle | Lamya Garabet Waleed Ghanima Anbjørg Rangberg Raul Teruel-Montoya Constantino Martinez Maria Luisa Lozano Camilla F. Nystrand James B. Bussel Per Morten Sandset Christine M. Jonassen Circulating microRNAs in patients with immune thrombocytopenia before and after treatment with thrombopoietin-receptor agonists Platelets itp micrornas tpo-ras |
| title | Circulating microRNAs in patients with immune thrombocytopenia before and after treatment with thrombopoietin-receptor agonists |
| title_full | Circulating microRNAs in patients with immune thrombocytopenia before and after treatment with thrombopoietin-receptor agonists |
| title_fullStr | Circulating microRNAs in patients with immune thrombocytopenia before and after treatment with thrombopoietin-receptor agonists |
| title_full_unstemmed | Circulating microRNAs in patients with immune thrombocytopenia before and after treatment with thrombopoietin-receptor agonists |
| title_short | Circulating microRNAs in patients with immune thrombocytopenia before and after treatment with thrombopoietin-receptor agonists |
| title_sort | circulating micrornas in patients with immune thrombocytopenia before and after treatment with thrombopoietin receptor agonists |
| topic | itp micrornas tpo-ras |
| url | http://dx.doi.org/10.1080/09537104.2019.1585527 |
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