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Targeted regulation of MiR-98 on E2F1 increases chemosensitivity of leukemia cells K562/A02

Authors Huang YD, Hong XL, Hu J, Lu Q

Received 5 November 2016

Accepted for publication 15 May 2017

Published 29 June 2017 Volume 2017:10 Pages 3233—3239

DOI https://doi.org/10.2147/OTT.S126819

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Ru Chen

Peer reviewer comments 3

Editor who approved publication: Dr Ingrid Espinoza

Yingdan Huang,1,2 Xiuli Hong,2 Jiasheng Hu,2 Quanyi Lu2

1
Department of Blood Transfusion, The First Affiliated Hospital of Xiamen University, 2Department of Hematology, Zhongshan Hospital of Xiamen University, Xiamen, People’s Republic of China

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.

Keywords: miRNA-98, leukemia cells, E2F1, drug resistance, K562/A02

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