MiR-7 Functions as a Tumor Suppressor by Targeting the Oncogenes TAL1 in T-Cell Acute Lymphoblastic Leukemia
Background: T-cell acute lymphoblastic leukemia is a hematologic malignancy characterized by T-cell proliferation, and in many cases, the ectopic expression of the oncogenic transcription factor T-cell acute lymphocytic leukemia protein 1 (TAL1). MicroRNA-7 has been shown to play a critical role in...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
SAGE Publishing
2020-07-01
|
| Series: | Technology in Cancer Research & Treatment |
| Online Access: | https://doi.org/10.1177/1533033820934130 |
| _version_ | 1818262711543267328 |
|---|---|
| author | Hongbo Sun MD Zhifu Zhang MD Wei Luo MD Junmin Liu MD Ye Lou MD Shengmei Xia MD |
| author_facet | Hongbo Sun MD Zhifu Zhang MD Wei Luo MD Junmin Liu MD Ye Lou MD Shengmei Xia MD |
| author_sort | Hongbo Sun MD |
| collection | DOAJ |
| description | Background: T-cell acute lymphoblastic leukemia is a hematologic malignancy characterized by T-cell proliferation, and in many cases, the ectopic expression of the oncogenic transcription factor T-cell acute lymphocytic leukemia protein 1 (TAL1). MicroRNA-7 has been shown to play a critical role in proliferation, migration, and treatment sensitivity in a diverse array of cancers. In this study, we sought to establish a novel link between microRNA-7 and T-cell acute lymphoblastic leukemia oncogenesis. Material and Method: To do so, we characterized gene expression of microRNA-7 as well as TAL1 in both T-cell acute lymphoblastic leukemia patient-derived tissue and cell lines, as well as performing functional luciferase assays to assess microRNA-7 binding to the TAL1 3′-untranslated region. We also performed growth, apoptosis, and migration experiments using 3-(4,5-dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide, Annexin V, and transwell assays in the context of microRNA-7 overexpression. Results: We found that microRNA-7 expression is attenuated and inversely correlated with TAL1 expression in TAL1 + T-cell acute lymphoblastic leukemia cells. Additionally, microRNA-7 directly targets and suppresses TAL1 levels. Finally, microRNA-7 overexpression reduces growth, motility, and migration while inducing apoptosis in T-cell acute lymphoblastic leukemia cells, phenotypes that can be rescued by concomitant overexpression of TAL1. Conclusions: These results indicate that microRNA-7 functions as a potent tumor suppressor by inhibiting the oncogene TAL1 and suggest microRNA-7 could function as a prognostic biomarker and possible therapeutic in the clinical management of T-cell acute lymphoblastic leukemia. |
| first_indexed | 2024-12-12T19:07:28Z |
| format | Article |
| id | doaj.art-08a8e9ed27e44f9ea88f95ac3eb32422 |
| institution | Directory Open Access Journal |
| issn | 1533-0338 |
| language | English |
| last_indexed | 2024-12-12T19:07:28Z |
| publishDate | 2020-07-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Technology in Cancer Research & Treatment |
| spelling | doaj.art-08a8e9ed27e44f9ea88f95ac3eb324222022-12-22T00:14:56ZengSAGE PublishingTechnology in Cancer Research & Treatment1533-03382020-07-011910.1177/1533033820934130MiR-7 Functions as a Tumor Suppressor by Targeting the Oncogenes TAL1 in T-Cell Acute Lymphoblastic LeukemiaHongbo Sun MD0Zhifu Zhang MD1Wei Luo MD2Junmin Liu MD3Ye Lou MD4Shengmei Xia MD5 Department of Hematology, Shenzhen Longhua People’s Hospital, Shenzhen, China Department of Hematology, Shenzhen Longhua People’s Hospital, Shenzhen, China Department of Hematology, Shenzhen Longhua People’s Hospital, Shenzhen, China Department of Hematology, Shenzhen Longhua People’s Hospital, Shenzhen, China Department of Hematology, Daqing Oilfield General Hospital, Daqing, China Department of Neurology, Shenzhen Longhua People’s Hospital, Shenzhen, ChinaBackground: T-cell acute lymphoblastic leukemia is a hematologic malignancy characterized by T-cell proliferation, and in many cases, the ectopic expression of the oncogenic transcription factor T-cell acute lymphocytic leukemia protein 1 (TAL1). MicroRNA-7 has been shown to play a critical role in proliferation, migration, and treatment sensitivity in a diverse array of cancers. In this study, we sought to establish a novel link between microRNA-7 and T-cell acute lymphoblastic leukemia oncogenesis. Material and Method: To do so, we characterized gene expression of microRNA-7 as well as TAL1 in both T-cell acute lymphoblastic leukemia patient-derived tissue and cell lines, as well as performing functional luciferase assays to assess microRNA-7 binding to the TAL1 3′-untranslated region. We also performed growth, apoptosis, and migration experiments using 3-(4,5-dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide, Annexin V, and transwell assays in the context of microRNA-7 overexpression. Results: We found that microRNA-7 expression is attenuated and inversely correlated with TAL1 expression in TAL1 + T-cell acute lymphoblastic leukemia cells. Additionally, microRNA-7 directly targets and suppresses TAL1 levels. Finally, microRNA-7 overexpression reduces growth, motility, and migration while inducing apoptosis in T-cell acute lymphoblastic leukemia cells, phenotypes that can be rescued by concomitant overexpression of TAL1. Conclusions: These results indicate that microRNA-7 functions as a potent tumor suppressor by inhibiting the oncogene TAL1 and suggest microRNA-7 could function as a prognostic biomarker and possible therapeutic in the clinical management of T-cell acute lymphoblastic leukemia.https://doi.org/10.1177/1533033820934130 |
| spellingShingle | Hongbo Sun MD Zhifu Zhang MD Wei Luo MD Junmin Liu MD Ye Lou MD Shengmei Xia MD MiR-7 Functions as a Tumor Suppressor by Targeting the Oncogenes TAL1 in T-Cell Acute Lymphoblastic Leukemia Technology in Cancer Research & Treatment |
| title | MiR-7 Functions as a Tumor Suppressor by Targeting the Oncogenes TAL1 in T-Cell Acute Lymphoblastic Leukemia |
| title_full | MiR-7 Functions as a Tumor Suppressor by Targeting the Oncogenes TAL1 in T-Cell Acute Lymphoblastic Leukemia |
| title_fullStr | MiR-7 Functions as a Tumor Suppressor by Targeting the Oncogenes TAL1 in T-Cell Acute Lymphoblastic Leukemia |
| title_full_unstemmed | MiR-7 Functions as a Tumor Suppressor by Targeting the Oncogenes TAL1 in T-Cell Acute Lymphoblastic Leukemia |
| title_short | MiR-7 Functions as a Tumor Suppressor by Targeting the Oncogenes TAL1 in T-Cell Acute Lymphoblastic Leukemia |
| title_sort | mir 7 functions as a tumor suppressor by targeting the oncogenes tal1 in t cell acute lymphoblastic leukemia |
| url | https://doi.org/10.1177/1533033820934130 |
| work_keys_str_mv | AT hongbosunmd mir7functionsasatumorsuppressorbytargetingtheoncogenestal1intcellacutelymphoblasticleukemia AT zhifuzhangmd mir7functionsasatumorsuppressorbytargetingtheoncogenestal1intcellacutelymphoblasticleukemia AT weiluomd mir7functionsasatumorsuppressorbytargetingtheoncogenestal1intcellacutelymphoblasticleukemia AT junminliumd mir7functionsasatumorsuppressorbytargetingtheoncogenestal1intcellacutelymphoblasticleukemia AT yeloumd mir7functionsasatumorsuppressorbytargetingtheoncogenestal1intcellacutelymphoblasticleukemia AT shengmeixiamd mir7functionsasatumorsuppressorbytargetingtheoncogenestal1intcellacutelymphoblasticleukemia |