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Published on: March 26, 2018
MicroRNA 34b inhibits cell proliferation in pediatric acute myeloid leukemia via regulating LDHA
1Department of Pediatrics, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huaian, China. kwx9743@163.com.
Objective:
To elucidate the regulatory effect of microRNA-34b on the occurrence of pediatric acute myeloid leukemia and the underlying mechanism.
Patients And Methods:
The expression of microRNA-34b in the bone marrow of 72 children with newly diagnosed acute myeloid leukemia (AML) was detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The relationship between microRNA-34b expression and pathological characteristics was analyzed. Kaplan-Meier curve was introduced for evaluating the prognostic value of microRNA-34b in pediatric AML. The regulatory effects of microRNA-34b on proliferation, cell cycle, and apoptosis of leukemia cells were accessed by cell counting kit-8 (CCK-8) assay and flow cytometry, respectively. Bioinformatics prediction and dual-luciferase reporter gene assay were conducted to evaluate the binding between microRNA-34b and lactate dehydrogenase A (LDHA). LDHA expression after overexpression of microRNA-34b was determined by qRT-PCR and Western blot. Rescue experiments were conducted to verify whether microRNA-34b could regulate proliferative and apoptotic behaviors of leukemia cells by suppressing LDHA expression.
Results:
MicroRNA-34b was markedly downregulated in AML children. Low expression of microRNA-34b was correlated to FAB typing, cytogenetic abnormality, and day 7 response to the treatment of pediatric AML. By collecting the follow-up data, it was found that low expression of microRNA-34b was correlated to the poor prognosis of AML. Overexpression of microRNA-34b inhibited proliferative ability and cell cycle progression, but accelerated apoptosis of AML cells. Dual-luciferase reporter gene assay verified that microRNA-34b could bind to LDHA, thereafter inhibiting LDHA expression. Overexpression of LDHA reversed the regulatory effects of microRNA-34b on proliferation, cell cycle, and apoptosis of AML cells.
Conclusions:
We found that microRNA-34b is lowly expressed in pediatric AML patients, and low expression of microRNA-34b may serve as an indicator of malignant progression and poor prognosis of pediatric AML. MicroRNA-34b may affect the proliferation and apoptosis of leukemia cells by regulating the expression of LDHA.
Insights
MicroRNA-34b is downregulated in pediatric acute myeloid leukemia (AML), indicating poor prognosis. This microRNA regulates leukemia cell proliferation and apoptosis by targeting lactate dehydrogenase A (LDHA).
Area of Science:
- Molecular Biology
- Oncology
- Genetics
Background:
- Pediatric acute myeloid leukemia (AML) is a significant health concern.
- Understanding the molecular mechanisms underlying AML is crucial for improving patient outcomes.
Purpose of the Study:
- To investigate the role of microRNA-34b in pediatric AML.
- To elucidate the regulatory effect of microRNA-34b on leukemia cell behavior and its underlying mechanism involving lactate dehydrogenase A (LDHA).
Main Methods:
- Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) to detect microRNA-34b expression in pediatric AML patients.
- Cell counting kit-8 (CCK-8) assay and flow cytometry to assess proliferation, cell cycle, and apoptosis.
- Bioinformatics prediction and dual-luciferase reporter gene assay to confirm the interaction between microRNA-34b and LDHA.
- Rescue experiments to validate the regulatory pathway.
Main Results:
- MicroRNA-34b expression was significantly downregulated in children with AML.
- Low microRNA-34b expression correlated with specific FAB typing, cytogenetic abnormalities, and poor treatment response.
- Reduced microRNA-34b levels were associated with a poorer prognosis in pediatric AML.
- Overexpression of microRNA-34b inhibited leukemia cell proliferation and cell cycle progression while promoting apoptosis.
- MicroRNA-34b directly targets and inhibits LDHA expression, and LDHA overexpression can reverse the effects of microRNA-34b on leukemia cells.
Conclusions:
- MicroRNA-34b is downregulated in pediatric AML and may serve as a prognostic biomarker.
- MicroRNA-34b influences leukemia cell proliferation and apoptosis by regulating LDHA expression.
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