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

Abstract

PurposeAcute 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 MethodsBone 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.ResultsmiR-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.ConclusionmiR-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.

Colon cancer-specific diagnostic and prognostic biomarkers based on genome-wide abnormal DNA methylation

“…We conducted in-depth KEGG and GO pathway enrichment analyses of the genes corresponding to the nine Hyper-DMPs and one Hypo-DMP, and we analyzed their protein-protein interactions in the STRING database. The leukemia inhibitory factor signaling pathway and the ciliary neurotrophic factor-mediated signaling pathway, both of which can activate the JAK2/STAT3 signaling pathway [ 34 , 35 ], were found to be enriched in our GO analysis. Coincidentally, the JAK/STAT pathway was found to be enriched in our KEGG pathway analysis.…”

Long non-coding RNA MALAT1 modulate cell migration, proliferation and apoptosis by sponging microRNA-146a to regulate CXCR4 expression in acute myeloid leukemia

“…In recent years, many scientists have focused on the roles of non-coding RNAs in AML development and therapy, including microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) [5]. MiRNAs are a class of single-stranded small non-coding RNAs with 19-22 nucleotides in length, which modulate gene expression at the post-transcriptional level via binding to the 3 ′untranslated regions of target genes [6]. Some studies found that microRNA-14a (miR-146a) was downregulated in some AML patients [7][8][9], which suggested miR-146a played a critical pathogenic role in AML.…”

MiRNA-146a rs2910164 Confers a Susceptibility to Digestive System Cancer: A Meta-Analysis Involving 59,098 Subjects

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