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Updated: Feb 26, 2026
Modeling Chemotherapy Resistant Leukemia In Vitro
Published on: February 9, 2016
Targeted regulation of MiR-98 on E2F1 increases chemosensitivity of leukemia cells K562/A02
Yingdan Huang1,2, Xiuli Hong2, Jiasheng Hu2
1Department of Blood Transfusion, The First Affiliated Hospital of Xiamen University.
Background:
miRNA is a microRNA that negatively regulates protein expression at post-transcriptional or translational level. It is widely involved in the pathogenesis of tumors. miR-98 belongs to the let-7 family, and its overexpression can increase the sensitivity to drugs in solid cancer cells. However, the function of miR-98 in leukemia is still unclear. In this study, the effect of miR-98 on drug resistance and proliferation of leukemia cells were investigated.
Methods:
Real-time quantitative polymerase chain reaction analyzed the expression difference between miR-98 and E2F1 in leukemia cell lines, K562 and K562/A02. The downstream target gene of miR-98 was predicted by TargetScan; K562/A02 was transiently transfected with miR-98 mimic to upregulate the expression of miR-98; real-time quantitative polymerase chain reaction and Western blot were used to analyze the expression alterations of E2F1; cell counting kit-8 was used to evaluate the influence on K562/A02 proliferation and sensitivity to chemotherapeutic drugs; meanwhile, Western blot was used to analyze the expression of p21, Bax, matrix metalloproteinase 9 and ABCG2 proteins.
Results:
E2F1 is one of the target genes of miR-98 proved by bioinformatics. Compared with the K562, the level of miRNA-98 expression was decreased in K562/A02, but the level of E2F1 expression was upregulated. Leukemia cell line K562/A02 was transfected with miR-98 mimic to upregulate the expression of miR-98, the expression of E2F1 was significantly decreased. After upregulating the miR-98 expression in K562/A02, the proliferation was weakened, and the sensitivity to chemotherapy was increased. Western blot showed that upregulated miR-98 expression increased the levels of p21 and BAX proteins in K562/A02 cells, and decreased the levels of matrix metalloprotease 9 and ABCG2 proteins, which were significantly different compared with those before miR-98 mimic transfection.
Conclusion:
In the leukemia drug-resistant cell line K562/A02, the targeted upregulated expression of miR-98 could decrease the proliferation of leukemia cells and improve the sensitivity to chemotherapeutics by inhibiting E2F1 expression. miR-98 might be a potential target for overcoming leukemia multidrug resistance.
Insights
Overexpressing microRNA-98 (miR-98) in leukemia cells inhibits proliferation and enhances chemotherapy sensitivity by targeting E2F1. This suggests miR-98 as a potential therapeutic target for overcoming multidrug resistance in leukemia.
Area of Science:
- Molecular Biology
- Oncology
- Genetics
Background:
- MicroRNAs (miRNAs) are key regulators of gene expression involved in cancer pathogenesis.
- While miR-98 enhances drug sensitivity in solid tumors, its role in leukemia remains largely unknown.
- This study investigates the function of miR-98 in leukemia drug resistance and cell proliferation.
Purpose of the Study:
- To determine the effect of miR-98 on the proliferation of leukemia cells.
- To investigate the impact of miR-98 on the sensitivity of leukemia cells to chemotherapeutic drugs.
- To elucidate the molecular mechanisms underlying miR-98's function in leukemia.
Main Methods:
- Real-time quantitative PCR and Western blot were used to analyze gene and protein expression levels.
- Bioinformatic prediction identified E2F1 as a potential target of miR-98.
- K562/A02 leukemia cells were transfected with miR-98 mimic to upregulate its expression, followed by proliferation and drug sensitivity assays.
Main Results:
- miR-98 expression was decreased, while E2F1 expression was upregulated in drug-resistant K562/A02 cells compared to K562 cells.
- Upregulating miR-98 in K562/A02 cells led to decreased E2F1 expression, reduced cell proliferation, and increased sensitivity to chemotherapy.
- miR-98 upregulation elevated p21 and BAX protein levels while decreasing matrix metalloproteinase 9 and ABCG2 levels.
Conclusions:
- Targeted upregulation of miR-98 inhibits leukemia cell proliferation and enhances chemosensitivity by suppressing E2F1 expression in drug-resistant cells.
- miR-98 demonstrates potential as a therapeutic target to overcome multidrug resistance in leukemia.
- The findings provide insights into the role of miR-98 in regulating key proteins involved in cell cycle, apoptosis, and drug resistance.
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