Related Experiment Video
Updated: May 23, 2025
Describing a Transcription Factor Dependent Regulation of the MicroRNA Transcriptome
Published on: June 15, 2016
Micro-RNA-140-3p Acts as a Tumor Suppressor Gene in Acute Promyelocytic Leukemia by Targeting Hepatocyte Growth
RuiQi Lei1, Xin Liu1, YiTing Wu1
1Division of Hematology, Department of Medicine, The First Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Nan Gang District, Harbin, Heilongjiang Province, 150001, China.
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.
Insights
MicroRNAs (miRNAs) regulate gene expression and are crucial in acute promyelocytic leukemia (APL). Upregulating miR-140-3p inhibits APL cell proliferation and promotes differentiation, offering therapeutic potential.
Area of Science:
- Molecular Biology
- Hematology
- Oncology
Background:
- MicroRNAs (miRNAs) are key regulators of gene expression post-transcriptionally.
- miRNAs play significant roles in hematopoietic stem cell differentiation and are implicated in acute promyelocytic leukemia (APL).
- Differential miRNA expression is observed in relapsed APL, with miR-140-3p notably downregulated.
Purpose of the Study:
- To investigate the role of miR-140-3p in APL.
- To identify direct target genes of miR-140-3p.
- To explore the therapeutic potential of modulating miR-140-3p in APL.
Main Methods:
- Dual luciferase assay to confirm direct targeting.
- Lentiviral transfection of NB4 cells to manipulate miR-140-3p expression.
- Flow cytometry and proliferation assays to assess cell behavior.
Main Results:
- Hepatocyte growth factor (HGF) was identified as a direct target gene of miR-140-3p.
- Low miR-140-3p expression inhibited NB4 cell differentiation and apoptosis while promoting proliferation and cell cycle progression.
- Upregulation of miR-140-3p suppressed proliferation, arrested the cell cycle, and enhanced apoptosis and differentiation in APL cells.
Conclusions:
- HGF is a direct target of miR-140-3p.
- miR-140-3p upregulation has anti-proliferative and pro-differentiation effects in APL cells.
- Monitoring miR-140-3p and HGF levels may predict APL recurrence risk, and targeting the miR-140-3p/HGF pathway shows therapeutic promise for recurrent APL.
Related Concept Videos
01:22MicroRNAs
02:23Abnormal Proliferation