Effect of miR-214 on Fludarabine Resistance in Chronic Lymphocytic Leukemia.
10.19746/j.cnki.issn.1009-2137.2019.05.007
- Author:
Zhi-Jian ZOU
1
;
Hong-Li SUN
1
;
Yun-Feng SHEN
1
;
Xin ZHOU
2
Author Information
1. Department of Hematology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi 214023, Jiangsu Province, China.
2. Department of Hematology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi 214023, Jiangsu Province, China,E-mail:13358111962@189.com.
- Publication Type:Journal Article
- MeSH:
Apoptosis;
Humans;
Leukemia, Lymphocytic, Chronic, B-Cell;
drug therapy;
MicroRNAs;
Phosphatidylinositol 3-Kinases;
Vidarabine;
analogs & derivatives;
genetics;
therapeutic use
- From:
Journal of Experimental Hematology
2019;27(5):1395-1401
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To investigate effect and mechanism of miR-214 in fludarabine resistance of chronic lympho-cytic leukemia (CLL).
METHODS: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.
RESULTS:The expression level of miR-214 in mononuclear cells of CLL patients significantly increased in comparison with healthy persons(P<0.05); the expression level of miR-214 in miR-214-ASO group significantly decreased (P<0.05); Absorbance in control group at Flu concentration of 3, 10 and 30 μmol/L was significantly decreased (P<0.05). Apoptosis rate in miR-214-ASO group at Flu concentration of 10 mmol/L significantly increased (P<0.05). At Flu concentration of 10 mmol/L, mRNA levels PTEN and BAD in miR-214-ASO group significantly increased (P<0.05), but mRNA levels of MDM2 and NF-κB significantly decreased (P<0.05). At Flu concentration of 10 mmol/L, protein levels of PTEN and p-BAD in miR-214-ASO group significantly increased (P<0.05), but protein levels of MDM2 and NF-κB significantly decreased (P<0.05).
CONCLUSION: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.
