Mechanism of miR-155 Promoting Drug Resistance in Childhood Acute Lymphoblastic Leukemia by Regulating Wnt/β-Catenin Signaling Pathway.
10.19746/j.cnki.issn.1009-2137.2022.02.016
- Author:
Hui-Min HUANG
1
;
Yun-Jian WEI
2
;
Dan WANG
1
;
Xiao-Mei WEN
3
Author Information
1. Department of Pediatrics, The First Affiliated Hospital of Hainan Medical University, Haikou 570100, Hainan Province, China.
2. Hainan Province Key Laboratory For Human Reproductive Medicine And Genetic Research, Haikou 570100, Hainan Province, China.
3. Department of Pediatrics, The First Affiliated Hospital of Hainan Medical University, Haikou 570100, Hainan Province, China,E-mail: 13707549628@126.com.
- Publication Type:Journal Article
- Keywords:
B acute lymphoblastic leukemia;
Wnt/β-Catenin;
chemoresistance;
children;
miR-155
- MeSH:
Apoptosis;
Cell Line, Tumor;
Cell Proliferation;
Child;
Cytarabine;
Drug Resistance, Neoplasm;
Gene Expression Regulation, Neoplastic;
Humans;
MicroRNAs/genetics*;
Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics*;
Wnt Signaling Pathway;
beta Catenin/genetics*
- From:
Journal of Experimental Hematology
2022;30(2):418-424
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To investigate the mechanism of miR-155 promoting drug resistance of children B-ALL to Ara-C by regulating Wnt/β-Catenin signaling pathway.
METHODS:The expression of miR-155 in bone marrow tissue and cell line of B-ALL was detected by PCR. The chemotherapy resistant strain REH/ Ara-C was constructed by using REH cells. REH/ Ara-C cells were transfected with miR-155 inhibitor. The proliferation of REH/Ara-C cells was detected by EdU. The apoptosis of REH/ Ara-C cells was detected by flow cytometry. The drug resistance of REH/Ara-C cells were analyzed by CCK-8 method and colony formation assay. The expression of Wnt/β-Catenin signaling pathway related proteins were determined by Western blot. MiR-155 inhibitor and Wnt activator agonist were used to transfect REH/Ara-C cells, and their effects on cell proliferation, apoptosis and drug resistance were determined.
RESULTS:Compared with normal tissues and cells, the expression level of miR-155 in B-ALL bone marrow tissue/cell line was increased (P<0.05); Compared with drug sensitive B-ALL tissues/cell lines, the expression level of miR-155 in drug resistant B-ALL tissues and cell lines was increased (P<0.05); Inhibition of miR-155 expression decreased the proliferation of REH/Ara-C cells (P<0.05), promoted apoptosis (P<0.05), enhanced the cytotoxicity of Ara-C (P<0.05), and inhibited Wnt/β-Catenin signaling pathway related protein and MDR1 gene expression (P<0.05), which could be reversed by activating Wnt expression (P<0.05).
CONCLUSION:The expression of miR-155 is up-regulated in bone marrow of children with B-ALL, which may be related to the activation of Wnt/β-Catenin signaling pathway promotes the proliferation of B-ALL cells and inhibits apoptosis, which leads to chemotherapy resistance.
