MiR-130a is aberrantly overexpressed in adult acute myeloid leukemia with t(8;21) and its suppression induces AML cell death
Background: Emerging evidence has revealed that miRNAs can function as oncogenes or tumor suppressor genes in leukemia. The ectopic expression of miR-130a has been reported in chronic leukemia, but our understanding of the biological implications of miR-130a expression remains incomplete. Methods: W...
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| Format: | Article |
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Upsala Medical Society
2018-01-01
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| Series: | Upsala Journal of Medical Sciences |
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| Online Access: | http://dx.doi.org/10.1080/03009734.2018.1440037 |
| _version_ | 1797699962574733312 |
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| author | Chao Ding Su-Ning Chen Roderick A. F. Macleod Hans G. Drexler Stefan Nagel De-Pei Wu Ai-Ning Sun Hai-Ping Dai |
| author_facet | Chao Ding Su-Ning Chen Roderick A. F. Macleod Hans G. Drexler Stefan Nagel De-Pei Wu Ai-Ning Sun Hai-Ping Dai |
| author_sort | Chao Ding |
| collection | DOAJ |
| description | Background: Emerging evidence has revealed that miRNAs can function as oncogenes or tumor suppressor genes in leukemia. The ectopic expression of miR-130a has been reported in chronic leukemia, but our understanding of the biological implications of miR-130a expression remains incomplete. Methods: We quantified a cohort of de novo acute myeloid leukemia (AML) by bead-based miRNA and real-time quantitative PCR (Rq-PCR). The luciferase reporter gene assay was analyzed after the plasmid constructs which contain 5’-UTR of miR-130a and a Renilla luciferase reporter plasmid were transfected simultaneously into 293T cells. MTT and caspase 3/7 apoptosis assays were used to test cell viability and apoptosis. Results: We identified miR-130a as significantly overexpressed in t(8;21) AML. Expression of miR-130a decreased significantly once patients with t(8;21) achieved complete remission, but increased sharply at the time of relapse. In patients with t(8;21) AML, KIT mutational status was associated with miR-130a expression—with higher expression associated with KIT activating mutations. Increased miR-130a expression in t(8;21) AML was associated with slightly worse event-free survival; however, no impact on overall survival was observed. Knockdown of AML1/ETO protein in the SKNO-1 cell line resulted in decrease of expression of miR-130a. Direct binding of AML1/ETO fusion protein with the promoter sequence of miR-130a was detected with luciferase reporter gene assay. Following miR-130a knockdown, SKNO-1 demonstrated increased sensitivity to etoposide. Conclusions: Our data suggest that miR-130a is directly activated by AML1/ETO, and may act as a factor which is associated with leukemia burden, event-free survival, and chemotherapy sensitivity in t(8;21) AML. |
| first_indexed | 2024-03-12T04:16:30Z |
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| id | doaj.art-d9a61acf99c746f9aab67c61241a5722 |
| institution | Directory Open Access Journal |
| issn | 0300-9734 2000-1967 |
| language | English |
| last_indexed | 2024-03-12T04:16:30Z |
| publishDate | 2018-01-01 |
| publisher | Upsala Medical Society |
| record_format | Article |
| series | Upsala Journal of Medical Sciences |
| spelling | doaj.art-d9a61acf99c746f9aab67c61241a57222023-09-03T10:38:05ZengUpsala Medical SocietyUpsala Journal of Medical Sciences0300-97342000-19672018-01-011231192710.1080/03009734.2018.14400371440037MiR-130a is aberrantly overexpressed in adult acute myeloid leukemia with t(8;21) and its suppression induces AML cell deathChao Ding0Su-Ning Chen1Roderick A. F. Macleod2Hans G. Drexler3Stefan Nagel4De-Pei Wu5Ai-Ning Sun6Hai-Ping Dai7Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow UniversityJiangsu Institute of Hematology, The First Affiliated Hospital of Soochow UniversityLeibniz Institute DSMZ–German Collection of Microorganisms and Cell CulturesLeibniz Institute DSMZ–German Collection of Microorganisms and Cell CulturesLeibniz Institute DSMZ–German Collection of Microorganisms and Cell CulturesJiangsu Institute of Hematology, The First Affiliated Hospital of Soochow UniversityJiangsu Institute of Hematology, The First Affiliated Hospital of Soochow UniversityJiangsu Institute of Hematology, The First Affiliated Hospital of Soochow UniversityBackground: Emerging evidence has revealed that miRNAs can function as oncogenes or tumor suppressor genes in leukemia. The ectopic expression of miR-130a has been reported in chronic leukemia, but our understanding of the biological implications of miR-130a expression remains incomplete. Methods: We quantified a cohort of de novo acute myeloid leukemia (AML) by bead-based miRNA and real-time quantitative PCR (Rq-PCR). The luciferase reporter gene assay was analyzed after the plasmid constructs which contain 5’-UTR of miR-130a and a Renilla luciferase reporter plasmid were transfected simultaneously into 293T cells. MTT and caspase 3/7 apoptosis assays were used to test cell viability and apoptosis. Results: We identified miR-130a as significantly overexpressed in t(8;21) AML. Expression of miR-130a decreased significantly once patients with t(8;21) achieved complete remission, but increased sharply at the time of relapse. In patients with t(8;21) AML, KIT mutational status was associated with miR-130a expression—with higher expression associated with KIT activating mutations. Increased miR-130a expression in t(8;21) AML was associated with slightly worse event-free survival; however, no impact on overall survival was observed. Knockdown of AML1/ETO protein in the SKNO-1 cell line resulted in decrease of expression of miR-130a. Direct binding of AML1/ETO fusion protein with the promoter sequence of miR-130a was detected with luciferase reporter gene assay. Following miR-130a knockdown, SKNO-1 demonstrated increased sensitivity to etoposide. Conclusions: Our data suggest that miR-130a is directly activated by AML1/ETO, and may act as a factor which is associated with leukemia burden, event-free survival, and chemotherapy sensitivity in t(8;21) AML.http://dx.doi.org/10.1080/03009734.2018.1440037Acute myeloid leukemiamiR-130at(8;21)outcomeoverexpression |
| spellingShingle | Chao Ding Su-Ning Chen Roderick A. F. Macleod Hans G. Drexler Stefan Nagel De-Pei Wu Ai-Ning Sun Hai-Ping Dai MiR-130a is aberrantly overexpressed in adult acute myeloid leukemia with t(8;21) and its suppression induces AML cell death Upsala Journal of Medical Sciences Acute myeloid leukemia miR-130a t(8;21) outcome overexpression |
| title | MiR-130a is aberrantly overexpressed in adult acute myeloid leukemia with t(8;21) and its suppression induces AML cell death |
| title_full | MiR-130a is aberrantly overexpressed in adult acute myeloid leukemia with t(8;21) and its suppression induces AML cell death |
| title_fullStr | MiR-130a is aberrantly overexpressed in adult acute myeloid leukemia with t(8;21) and its suppression induces AML cell death |
| title_full_unstemmed | MiR-130a is aberrantly overexpressed in adult acute myeloid leukemia with t(8;21) and its suppression induces AML cell death |
| title_short | MiR-130a is aberrantly overexpressed in adult acute myeloid leukemia with t(8;21) and its suppression induces AML cell death |
| title_sort | mir 130a is aberrantly overexpressed in adult acute myeloid leukemia with t 8 21 and its suppression induces aml cell death |
| topic | Acute myeloid leukemia miR-130a t(8;21) outcome overexpression |
| url | http://dx.doi.org/10.1080/03009734.2018.1440037 |
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