miR-22-3p Negatively Affects Tumor Progression in T-Cell Acute Lymphoblastic Leukemia
T-cell acute lymphoblastic leukemia (T-ALL) is a rare, aggressive disease arising from T-cell precursors. NOTCH1 plays an important role both in T-cell development and leukemia progression, and more than 60% of human T-ALLs harbor mutations in components of the NOTCH1 signaling pathway, leading to d...
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MDPI AG
2020-07-01
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| Online Access: | https://www.mdpi.com/2073-4409/9/7/1726 |
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| author | Valentina Saccomani Angela Grassi Erich Piovan Deborah Bongiovanni Ludovica Di Martino Sonia Minuzzo Valeria Tosello Paola Zanovello |
| author_facet | Valentina Saccomani Angela Grassi Erich Piovan Deborah Bongiovanni Ludovica Di Martino Sonia Minuzzo Valeria Tosello Paola Zanovello |
| author_sort | Valentina Saccomani |
| collection | DOAJ |
| description | T-cell acute lymphoblastic leukemia (T-ALL) is a rare, aggressive disease arising from T-cell precursors. NOTCH1 plays an important role both in T-cell development and leukemia progression, and more than 60% of human T-ALLs harbor mutations in components of the NOTCH1 signaling pathway, leading to deregulated cell growth and contributing to cell transformation. Besides multiple NOTCH1 target genes, microRNAs have also been shown to regulate T-ALL initiation and progression. Using an established mouse model of T-ALL induced by NOTCH1 activation, we identified several microRNAs downstream of NOTCH1 activation. In particular, we found that NOTCH1 inhibition can induce miR-22-3p in NOTCH1-dependent tumors and that this regulation is also conserved in human samples. Importantly, miR-22-3p overexpression in T-ALL cells can inhibit colony formation in vitro and leukemia progression in vivo. In addition, miR-22-3p was found to be downregulated in T-ALL specimens, both T-ALL cell lines and primary samples, relative to immature T-cells. Our results suggest that miR-22-3p is a functionally relevant microRNA in T-ALL whose modulation can be exploited for therapeutic purposes to inhibit T-ALL progression. |
| first_indexed | 2024-03-10T18:23:33Z |
| format | Article |
| id | doaj.art-3ca3afc6952e48418d0b83c6d3708853 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T18:23:33Z |
| publishDate | 2020-07-01 |
| publisher | MDPI AG |
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| spelling | doaj.art-3ca3afc6952e48418d0b83c6d37088532023-11-20T07:12:43ZengMDPI AGCells2073-44092020-07-0197172610.3390/cells9071726miR-22-3p Negatively Affects Tumor Progression in T-Cell Acute Lymphoblastic LeukemiaValentina Saccomani0Angela Grassi1Erich Piovan2Deborah Bongiovanni3Ludovica Di Martino4Sonia Minuzzo5Valeria Tosello6Paola Zanovello7Department of Surgery, Oncology and Gastroenterology, Immunology & Oncology Section, University of Padova, 35128 Padua, ItalyImmunology and Molecular Oncology Unit, Veneto Institute of Oncology IOV—IRCCS, 35128 Padua, ItalyDepartment of Surgery, Oncology and Gastroenterology, Immunology & Oncology Section, University of Padova, 35128 Padua, ItalyDepartment of Surgery, Oncology and Gastroenterology, Immunology & Oncology Section, University of Padova, 35128 Padua, ItalyDepartment of Surgery, Oncology and Gastroenterology, Immunology & Oncology Section, University of Padova, 35128 Padua, ItalyDepartment of Surgery, Oncology and Gastroenterology, Immunology & Oncology Section, University of Padova, 35128 Padua, ItalyImmunology and Molecular Oncology Unit, Veneto Institute of Oncology IOV—IRCCS, 35128 Padua, ItalyDepartment of Surgery, Oncology and Gastroenterology, Immunology & Oncology Section, University of Padova, 35128 Padua, ItalyT-cell acute lymphoblastic leukemia (T-ALL) is a rare, aggressive disease arising from T-cell precursors. NOTCH1 plays an important role both in T-cell development and leukemia progression, and more than 60% of human T-ALLs harbor mutations in components of the NOTCH1 signaling pathway, leading to deregulated cell growth and contributing to cell transformation. Besides multiple NOTCH1 target genes, microRNAs have also been shown to regulate T-ALL initiation and progression. Using an established mouse model of T-ALL induced by NOTCH1 activation, we identified several microRNAs downstream of NOTCH1 activation. In particular, we found that NOTCH1 inhibition can induce miR-22-3p in NOTCH1-dependent tumors and that this regulation is also conserved in human samples. Importantly, miR-22-3p overexpression in T-ALL cells can inhibit colony formation in vitro and leukemia progression in vivo. In addition, miR-22-3p was found to be downregulated in T-ALL specimens, both T-ALL cell lines and primary samples, relative to immature T-cells. Our results suggest that miR-22-3p is a functionally relevant microRNA in T-ALL whose modulation can be exploited for therapeutic purposes to inhibit T-ALL progression.https://www.mdpi.com/2073-4409/9/7/1726miR-22-3pT-ALLNOTCH1 |
| spellingShingle | Valentina Saccomani Angela Grassi Erich Piovan Deborah Bongiovanni Ludovica Di Martino Sonia Minuzzo Valeria Tosello Paola Zanovello miR-22-3p Negatively Affects Tumor Progression in T-Cell Acute Lymphoblastic Leukemia Cells miR-22-3p T-ALL NOTCH1 |
| title | miR-22-3p Negatively Affects Tumor Progression in T-Cell Acute Lymphoblastic Leukemia |
| title_full | miR-22-3p Negatively Affects Tumor Progression in T-Cell Acute Lymphoblastic Leukemia |
| title_fullStr | miR-22-3p Negatively Affects Tumor Progression in T-Cell Acute Lymphoblastic Leukemia |
| title_full_unstemmed | miR-22-3p Negatively Affects Tumor Progression in T-Cell Acute Lymphoblastic Leukemia |
| title_short | miR-22-3p Negatively Affects Tumor Progression in T-Cell Acute Lymphoblastic Leukemia |
| title_sort | mir 22 3p negatively affects tumor progression in t cell acute lymphoblastic leukemia |
| topic | miR-22-3p T-ALL NOTCH1 |
| url | https://www.mdpi.com/2073-4409/9/7/1726 |
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