microRNA-146a Promotes Growth of Acute Leukemia Cells by Downregulating Ciliary Neurotrophic Factor Receptor and Activating JAK2/STAT3 Signaling
10.3349/ymj.2019.60.10.924
- Author:
Lei WANG
1
;
Hongyan ZHANG
;
Donghong LEI
Author Information
1. Department of Pediatrics, Jinan Second Maternal and Child Health Hospital, Jinan, Shandong, China.
- Publication Type:Original Article
- Keywords:
miR-146a;
acute leukemia;
CNTFR;
JAK/STAT pathway
- MeSH:
Apoptosis;
Blotting, Western;
Bone Marrow;
Cell Proliferation;
Child;
Ciliary Neurotrophic Factor;
Flow Cytometry;
Genes, Reporter;
HL-60 Cells;
Humans;
Karyotype;
Leukemia;
Leukemia, Myeloid, Acute;
Luciferases;
Precursor Cell Lymphoblastic Leukemia-Lymphoma;
Real-Time Polymerase Chain Reaction;
Receptor, Ciliary Neurotrophic Factor
- From:Yonsei Medical Journal
2019;60(10):924-934
- CountryRepublic of Korea
- Language:English
-
Abstract:
PURPOSE: Acute leukemia (AL) is classified as acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). This study aimed to investigate the effect of miR-146a on childhood AL and its underlying molecular mechanisms. MATERIALS AND METHODS: Bone marrow samples were obtained from 39 AL children and 10 non-cancer controls. The expressions of miR-146a and ciliary neurotrophic factor receptor (CNTFR) were detected by quantitative real-time polymerase chain reaction (qRT-PCR) in ALL and AML pediatric patients, as well as ALL (Jurkat) and AML (HL-60) cells. Correlations between miR-146a and clinical indicators were explored. A targeting relationship between miR-146a and CNTFR was detected by dual luciferase reporter gene assay. Cell proliferation, apoptosis, migration, and invasion of Jurkat and HL-60 cells were measured by MTT assay, flow cytometry, and transwell assay, respectively. LIF expression was detected by qRT-PCR in Jurkat and HL-60 cells. The expression of p-JAK2, JAK2, p-STAT3, and STAT3 in HL-60 cells was measured by Western blot. RESULTS: miR-146a was increased in ALL and AML pediatric patients, while CNTFR was decreased. miR-146a expression was associated with immunophenotype, karyotype, fusion gene, and SIL-TAL1. CNTFR was a target gene of miR-146a. miR-146a could promote cell proliferation, migration, and invasion, as well as inhibit cell apoptosis in Jurkat and HL-60 cells by downregulating CNTFR. Meanwhile, miR-146a inhibited the expression of LIF and activated JAK2/STAT3 pathway by downregulating CNTFR. CONCLUSION: miR-146a could promote the proliferation, migration, and invasion and inhibit the apoptosis of AL Jurkat and HL-60 cells by downregulating CNTFR and activating the JAK2/STAT3 pathway.
