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miR-302 cluster inhibits angiogenesis and growth of K562 leukemia cells by targeting VEGFA

Authors Cao J, Li L, Han X, Cheng H, Chen W, Qi K, Chen C, Wu Q, Niu M, Zeng L, Xu K

Received 8 October 2018

Accepted for publication 21 November 2018

Published 8 January 2019 Volume 2019:12 Pages 433—441

DOI https://doi.org/10.2147/OTT.S190146

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Cristina Weinberg

Peer reviewer comments 3

Editor who approved publication: Dr Leo Jen-Liang Su


Jiang Cao,1,* Li Li,2,* Xiao Han,1 Hai Cheng,1 Wei Chen,1 Kunming Qi,1 Chong Chen,1 Qingyun Wu,1 Mingshan Niu,1 Lingyu Zeng,1 Kailin Xu1

1Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, China; 2Department of Gastroenterology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, China

*These authors contributed equally to this work

Background: miR-302 cluster has been reported as a tumor suppressor in many human cancers; yet, its function in chronic myeloid leukemia (CML) tumorigenesis remains largely unclear. The study was aimed to explore the functional roles of miR-302 cluster in CML progression.
Materials and methods: Quantitative reverse transcriptase PCR and Western blot were performed to evaluate miR-302 cluster and vascular endothelial growth factor A (VEGFA) expression levels. Cell Counting Kit-8 assay, colony formation assay and human umbilical vein endothelial cell line capillary tube formation were used to determine the influence of miR-302 cluster on the growth and angiogenesis of K562 cells, respectively. Luciferase reporter assay was employed to confirm the direct target interaction between miR-302 cluster and VEGFA.
Results: This study demonstrated that miR-302 cluster was frequently downregulated in CML samples and cell lines and high level of miR-302 cluster was significantly associated with good prognosis of CML patients. Compared with miRNA negative control, miR-302 cluster mimics obviously suppressed cell growth, colony formation and angiogenesis. Further studies revealed that VEGFA was a direct target gene of miR-302 cluster. Moreover, overexpression of VEGFA dramatically abated the inhibition of miR-302 cluster on cell growth and angiogenesis.
Conclusion: The present study, for the first time, identified miR-302 cluster as a tumor suppressor, and overexpression of miR-302 cluster inhibited growth and angiogenesis in K562 cells. miR-302 cluster may be a potential therapeutic target in CML to develop the adjuvant antiangiogenic therapy based on VEGFA.

Keywords: chronic myeloid leukemia, angiogenesis, miR-302, VEGFA

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