| Autor: |
Zhi-Jian, Zou, Hong-Li, Sun, Yun-Feng, Shen, Xin, Zhou |
| Rok vydání: |
2019 |
| Předmět: |
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| Zdroj: |
Zhongguo shi yan xue ye xue za zhi. 27(5) |
| ISSN: |
1009-2137 |
| Popis: |
To investigate effect and mechanism of miR-214 in fludarabine resistance of chronic lympho-cytic leukemia (CLL).A total of 10 patients with CLL resistante to fludarabine (Flu) and 10 healthy persons admitted to Hematology Department of our hospital in August 2014 - July 2018 were selected. Expression level of miR-214 in mononuclear cells in patients with CLL and healthy persons were determined by RT-PCR. Primary CLL cells from patients with CLL were divided into normal control group (control group), negative control group (miR-214-NC group) and viral transinfection group (miR-214-ASO group). After 24 h-transfection, CLL cells were cultured with different con-centration of Flu for 48 h, then the cell proliferation and apoptosis were detected, and the levels of down-stream genes and proteins releted with PTEN and PI3K/AKT signialing pathway were determined.The expression level of miR-214 in mononuclear cells of CLL patients significantly increased in comparison with healthy persons(P0.05); the expression level of miR-214 in miR-214-ASO group significantly decreased (P0.05); Absorbance in control group at Flu concentration of 3, 10 and 30 μmol/L was significantly decreased (P0.05). Apoptosis rate in miR-214-ASO group at Flu concentration of 10 mmol/L significantly increased (P0.05). At Flu concentration of 10 mmol/L, mRNA levels PTEN and BAD in miR-214-ASO group significantly increased (P0.05), but mRNA levels of MDM2 and NF-κB significantly decreased (P0.05). At Flu concentration of 10 mmol/L, protein levels of PTEN and p-BAD in miR-214-ASO group significantly increased (P0.05), but protein levels of MDM2 and NF-κB significantly decreased (P0.05).Inhibition of miR-214 can enhance the sensitivity of drug-resistant CLL cells to fludarabine, which may be raleted with the promotion of cell apotosis and regulation of down-stream molecules expression of PTEN/AKT signaling pathway.miR-214介导慢性淋巴细胞白血病对氟达拉滨耐药的作用研究.探讨miR-214在慢性淋巴细胞白血病（CLL）细胞对氟达拉滨耐药中的作用及机制.选择2014年08月-2018年07月本院血液科收治对氟达拉滨（Flu）耐药的CLL患者和健康受试者各10例，采用RT-PCR法测定单个核细胞中miR-214表达水平。将CLL患者原代细胞分为空白对照组（control group）、阴性对照组（miR-214-NC group）和miR-214转染组（miR-214-ASO group）。转染病毒24 h后与Flu共同培养48 h，测定细胞增殖和凋亡情况，以及PTEN和PI3K/AKT信号通路下游相关基因和蛋白表达水平.CLL患者单个核细胞miR-214的表达水平较健康受试者显著升高（P0.05）； miR-214转染组细胞miR-214表达水平显著降低（P0.05）； miR-214转染组细胞在Flu浓度为3、10和30 μmol/L时的吸光度显著降低（P0.05）； Flu浓度为10 mmol/L时miR-214转染组细胞的凋亡率显著增高（P0.05）， PTEN和BAD mRNA水平显著增高（P0.05），MDM2和NF-κB mRNA水平显著降低（P0.05），PTEN和p-BAD 蛋白水平显著增高（P0.05），MDM2和NF-κB 蛋白水平显著降低（P0.05）.抑制miR-214可以提高耐药的CLL细胞对氟达拉滨的敏感性，这种作用可能与其促进细胞凋亡有关，并且与其调节PTEN/AKT信号通路下游分子表达有关. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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