INTRODUCTION: T-cell acute lymphoblastic leukemia (T-ALL) is caused by a defect in T-cell maturation to the mature T cell. T-ALL is a poor prognostic hematopoietic malignancy. In order to establish a successful therapeutic treatment plan, it is essential to understand the biology of T-cell development and molecules that contribute to this process. This study uses Jurkat T cells, as a well-established model for in vitro study of T-ALL to investigate the role of the microRNA (miRNA), miR-146a, on gene expressions involved in T-cell differentiation. MATERIALS AND METHODS: The permanent over-expression of miR-146a was established using a lentivector that expressed GFP hsa-mir-146a miRNA. We used quantitative real-time polymerase chain reaction and flow cytometry for T-cell differentiation to monitor induction of the differentiation process by assessing changes in expression of some distinct transcription factors and cell surface markers. RESULTS: Ectopic expression of miR-146a resulted in significant up-regulation of PU.1, c-Fos, CCAAT/enhancer-binding protein alpha (C/EBPα) and GATA3, and slight up-regulation of Foxp3 and Runx1. There was a significant, moderate down-regulation in the expressions of Notch1, LIM-domain only (Lmo2), son of sevenless 1 (SOS1), Ikaros, and signal transducer and activator of transcription 3 (STAT3). CONCLUSION: Our results indicated that ectopic expression of miR-146a could not independently induce differentiation in lymphoblastic cells. However, the expression of multiple genes involved in T-cell differentiation and T-cell CD markers were found to be affected. These results have suggested a potential tumor suppressive, immunomodulatory and cell activator role for miR146-a.
INTRODUCTION: T-cell acute lymphoblastic leukemia (T-ALL) is caused by a defect in T-cell maturation to the mature T cell. T-ALL is a poor prognostic hematopoietic malignancy. In order to establish a successful therapeutic treatment plan, it is essential to understand the biology of T-cell development and molecules that contribute to this process. This study uses Jurkat T cells, as a well-established model for in vitro study of T-ALL to investigate the role of the microRNA (miRNA), miR-146a, on gene expressions involved in T-cell differentiation. MATERIALS AND METHODS: The permanent over-expression of miR-146a was established using a lentivector that expressed GFP hsa-mir-146a miRNA. We used quantitative real-time polymerase chain reaction and flow cytometry for T-cell differentiation to monitor induction of the differentiation process by assessing changes in expression of some distinct transcription factors and cell surface markers. RESULTS: Ectopic expression of miR-146a resulted in significant up-regulation of PU.1, c-Fos, CCAAT/enhancer-binding protein alpha (C/EBPα) and GATA3, and slight up-regulation of Foxp3 and Runx1. There was a significant, moderate down-regulation in the expressions of Notch1, LIM-domain only (Lmo2), son of sevenless 1 (SOS1), Ikaros, and signal transducer and activator of transcription 3 (STAT3). CONCLUSION: Our results indicated that ectopic expression of miR-146a could not independently induce differentiation in lymphoblastic cells. However, the expression of multiple genes involved in T-cell differentiation and T-cell CD markers were found to be affected. These results have suggested a potential tumor suppressive, immunomodulatory and cell activator role for miR146-a.
Entities:
Keywords:
Jurkat; T cell; differentiation; miR-146a
Authors: Haolong Qi; Shanshan Wang; Juekun Wu; Shucai Yang; Steven Gray; Calvin S H Ng; Jing Du; Malcolm J Underwood; Ming-Yue Li; George G Chen Journal: Ther Adv Med Oncol Date: 2019-06-13 Impact factor: 8.168