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The Expression of miRNA-26 during ATRA-induced Differentiation of HL-60 Cells Towards Granulocytes

Author: XiaoSheng
Tutor: FanZiLi
School: Central South University
Course: Department of Hematology
Keywords: HL-60 Cell Differentiation miRNA All-trans retinoic acid
CLC: R733.7
Type: Master's thesis
Year: 2010
Downloads: 110
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Abstract


Background: Acute myeloid leukemia (AML) is a group of clinical and biological behavior of a high degree of heterogeneity of the disease. AML occurs by the uncontrolled proliferation of myeloid white blood cells, differentiation and apoptosis induced disorder, which involves a series of genetic changes, such as chromosomal translocations, rearrangements, point mutations, deletions, gene modification, such as methylation, causes the activation of oncogenes and tumor suppressor gene inactivation. In recent years, as people's in-depth understanding of epigenetics, especially demethylation agent azacitidine (azacitidine) and its deoxy derivatives of 5 - aza-2'-deoxycytidine (5-Aza-2 '-deoxycytidine) success in the treatment of cancer patients clinical application of epigenetic cancer research has become a hot spot. MicroRNA (miRNA); biological endogenous length of about 18-25 nucleotides small non-coding RNA, through epigenetic regulation of the organism's normal way of growth, development, aging, death, and pathological processes. As a widespread problem of fine-tuning of gene expression molecules in acute myeloid proliferation and differentiation of leukocytes significance in recent years began to receive attention. Re-differentiation of leukemic cells induced leukemia is one of the main strategies, the use of all-trans retinoic acid (all-trans retinoic acid, ATRA) can make 70-80% of acute promyelocytic leukemia (acute promyelocytic leukemia, APL ) in patients with complete remission, and chemotherapy receive long-term remission, there may even be cured. The APL miRNAs involved in the regulation of cell differentiation mechanisms are not completely understood, especially for the PML-RARa fusion gene-negative acute myeloid leukemia cells. Therefore, this experiment using real-time fluorescence quantitative polymerase chain reaction (real-time fluorescence quantitative polymerase chain reaction, real-time PCR) for miR-26 in the ATRA-induced acute myeloid leukemia cells HL-60 myeloid differentiation expression studies to understand the regulation of miR-26 in the differentiation process of the mechanisms and provide experimental evidence. Objective: To investigate the all-trans retinoic acid (ATRA)-induced differentiation of HL-60 cells for miR-26 expression. Methods: all-trans retinoic acid (1μM) at different times under the influence of HL-60 cells to detect objects, using morphological changes observed under the microscope; flow cytometry cell surface differentiation marker CD15; Real-time PCR detection of different period miR-26 expression changes. Results: 1) With the drug-induced time, by HL-60 cells induced to myeloid differentiation, and the emergence of nuclear shape changes; 2) Compared with control group, ATRA role of 3d, 4d, 5d and 6d, the Flow cytometry differentiation of HL-60 cells, respectively (52.39 ± 3.56)%, (77.65 ± 0.24)%, (83.90 ± 1.30)%, (68.13 ± 1.67)%, (P lt; 0.01); 3) Real-timePCR detect miR-26A, miR-26B expression levels, 5d when the expression level increased significantly, miR-26A, miR-26B expression difference was statistically significant (P lt; 0.05). CONCLUSION: miR-26A, miR-26B in HL-60 cells induced by ATRA myeloid differentiation was significantly increased, suggesting that miR-26 may be involved in acute myeloid leukemia cells of myeloid differentiation regulation.

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CLC: > Medicine, health > Oncology > Hematopoietic and lymphoid neoplasms > Leukemia
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