Yonsei Med J.  2019 Oct;60(10):924-934. 10.3349/ymj.2019.60.10.924.

microRNA-146a Promotes Growth of Acute Leukemia Cells by Downregulating Ciliary Neurotrophic Factor Receptor and Activating JAK2/STAT3 Signaling

Affiliations
  • 1Department of Pediatrics, Jinan Second Maternal and Child Health Hospital, Jinan, Shandong, China.
  • 2Department of Pediatrics, Jinan First People's Hospital, Jinan, Shandong, China.
  • 3Department of Pediatrics II, Yulin First Hospital, Suide, Shaanxi, China. leidonghong21@163.com

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.

Keyword

miR-146a; acute leukemia; CNTFR; JAK/STAT pathway

MeSH Terms

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*
Ciliary Neurotrophic Factor
Luciferases
Receptor, Ciliary Neurotrophic Factor
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