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Published on: October 14, 2016
MiR-99a may serve as a potential oncogene in pediatric myeloid leukemia
Lidan Zhang, Xiaojuan Li, Zhiyong Ke
1Department of Pediatric, The First Affiliated Hospital of Sun Yat-Sen University, Zhongshan Er Lu, Guangzhou 510080, China. huazhang420@gmail.com.
Background:
Leukemia is the most common malignant proliferative disease in children. Our previous study found that miR-99a was up-regulated in pediatric primary AML using microRNA expression profiles. Up to date, although there is a certain number of reports on microRNA expression features and functions in pediatric acute myeloid leukemia (AML) and chronic myeloid leukemia (CML), the expression and function of miR-99a in these diseases remain to be investigated.
Methods:
qRT-PCR was performed to measure the expression level of miR-99a in 88 samples including 68 pediatric acute myeloid leukemia patients, 8 chronic myeloid leukemia patients and 12 pediatric controls. MTT assay, apoptosis assay, dual-luciferase reporter transfection assay and western blot analysis were used to investigate the function of miR-99a.
Results:
MiR-99a was highly expressed in pediatric-onset AML (M1-M5) and CML, while significantly lowly expressed during complete remission of these diseases. MTT assay indicated that the proliferations of K562 and HL60 cells were significantly promoted by miR-99a, and apoptosis assessment by Annexin V/propidium iodide staining demonstrated that the apoptosis of these cells was inhibited by miR-99a. Additionally, dual-luciferase reporter transfection assay and western blot analysis indicated that miR-99a may target CTDSPL and TRIB2, which are two tumor suppressor genes.
Conclusions:
This study revealed that miR-99a may play a potential oncogenic role in pediatric myeloid leukemia including AML and CML via regulating tumor suppressors CTDSPL and TRIB2, suggesting that these two leukemias might share some common biological pathways involved in the generation and development of disease and miR-99a could be a common therapeutic target for myeloid leukemias treatment.
Insights
MicroRNA-99a (miR-99a) is highly expressed in pediatric myeloid leukemias, promoting cancer cell growth and inhibiting apoptosis. This suggests miR-99a is a potential therapeutic target for acute myeloid leukemia (AML) and chronic myeloid leukemia (CML).
Area of Science:
- Hematology
- Molecular Biology
- Oncology
Background:
- Leukemia is a prevalent childhood malignancy.
- Previous studies identified miR-99a dysregulation in pediatric acute myeloid leukemia (AML).
- The specific role of miR-99a in pediatric AML and chronic myeloid leukemia (CML) requires further investigation.
Purpose of the Study:
- To investigate the expression and function of miR-99a in pediatric myeloid leukemias.
- To explore the potential oncogenic role of miR-99a and its molecular targets.
Main Methods:
- Quantitative reverse transcription polymerase chain reaction (qRT-PCR) for miR-99a expression analysis.
- Cell proliferation (MTT assay) and apoptosis (Annexin V/propidium iodide staining) assays.
- Dual-luciferase reporter assays and western blot analysis to identify miR-99a targets.
Main Results:
- miR-99a was significantly upregulated in pediatric AML and CML, and downregulated during remission.
- miR-99a promoted proliferation and inhibited apoptosis in K562 and HL60 leukemia cell lines.
- miR-99a potentially targets tumor suppressor genes CTDSPL and TRIB2.
Conclusions:
- miR-99a exhibits oncogenic activity in pediatric myeloid leukemias by regulating CTDSPL and TRIB2.
- Pediatric AML and CML may share common disease pathways involving miR-99a.
- miR-99a represents a potential common therapeutic target for myeloid leukemias.
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