Micro-RNA-140-3p Acts as a Tumor Suppressor Gene in Acute Promyelocytic Leukemia by Targeting Hepatocyte Growth Factor.

Abstract

MicroRNAs (miRNAs) are noncoding RNAs that regulate the expression of target genes after transcription, and play important roles in the differentiation of hematopoietic stem cells. Many miRNAs are related to the occurrence of acute promyelocytic leukemia (APL) and play roles in the treatment response. Recently, we demonstrated that several miRNAs are differentially expressed in patients with relapsed and newly diagnosed APL; for example, miR-140-3p is significantly downregulated in patients with relapsed APL. In this study, via a dual luciferase assay, we verified that one of the direct target genes of miR-140-3p is hepatocyte growth factor (HGF). After different lentiviruses were transfected into NB4 cells, and flow cytometry and proliferation assays confirmed that low expression of miR-140-3p inhibited the differentiation and apoptosis of NB4 cells and induced proliferation by promoting cell cycle progression. In summary, our findings suggest that hepatocyte growth factor is a target gene of miR-140-3p. Moreover, upregulation of miR-140-3p expression in APL cells inhibits cell proliferation, arrests cell cycle progression, and promotes apoptosis and cell differentiation. Monitoring the levels of miR-140-3p and HGF may predict the risk of disease recurrence, and interfering with the miR-140-3p / HGF pathway may have therapeutic potential for treating recurrent APL.