microRNA-146a Promotes Growth of Acute Leukemia Cells by Downregulating Ciliary Neurotrophic Factor Receptor and Activating JAK2/STAT3 Signaling
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Purpose: Acute leukemia (AL) is classified as acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). This studyaimed 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 expressionsof 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-146aand clinical indicators were explored. A targeting relationship between miR-146a and CNTFR was detected by dual luciferase reportergene assay. Cell proliferation, apoptosis, migration, and invasion of Jurkat and HL-60 cells were measured by MTT assay, flowcytometry, and transwell assay, respectively. LIF expression was detected by qRT-PCR in Jurkat and HL-60 cells. The expression ofp-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 associatedwith immunophenotype, karyotype, fusion gene, and SIL-TAL1. CNTFR was a target gene of miR-146a. miR-146a could promotecell 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-60cells by downregulating CNTFR and activating the JAK2/STAT3 pathway.
Abstract
Purpose: Acute leukemia (AL) is classified as acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). This studyaimed 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 expressionsof 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-146aand clinical indicators were explored. A targeting relationship between miR-146a and CNTFR was detected by dual luciferase reportergene assay. Cell proliferation, apoptosis, migration, and invasion of Jurkat and HL-60 cells were measured by MTT assay, flowcytometry, and transwell assay, respectively. LIF expression was detected by qRT-PCR in Jurkat and HL-60 cells. The expression ofp-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 associatedwith immunophenotype, karyotype, fusion gene, and SIL-TAL1. CNTFR was a target gene of miR-146a. miR-146a could promotecell 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-60cells by downregulating CNTFR and activating the JAK2/STAT3 pathway.
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