Back to Journals » OncoTargets and Therapy » Volume 9

Inhibition of microRNA-126 promotes the expression of Spred1 to inhibit angiogenesis in hepatocellular carcinoma after transcatheter arterial chemoembolization: in vivo study

Authors Ji J, Xu M, Song J, Zhao Z, Chen M, Chen W, Tu J, Yang X

Received 16 February 2016

Accepted for publication 16 May 2016

Published 19 July 2016 Volume 2016:9 Pages 4357—4367

DOI https://doi.org/10.2147/OTT.S106513

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Ashok Kumar Pandurangan

Peer reviewer comments 4

Editor who approved publication: Dr Jianmin Xu


Jian-Song Ji,1,2,* Min Xu,1,* Jing-Jing Song,1,* Zhong-Wei Zhao,1,* Min-Jiang Chen,1 Wei-Qian Chen,1 Jian-Fei Tu,1 Xiao-Ming Yang2

1Department of Radiology, Affiliated Lishui Hospital of Zhejiang University, Fifth Affiliated Hospital of Wenzhou Medical University, Central Hospital of Zhejiang Lishui, Lishui, People’s Republic of China; 2Department of Radiology, Lab-Yang, University of Washington, Seattle, WA, USA

*These authors contributed equally to this work

Abstract: MicroRNA-126 (miR-126) has been found to promote angiogenesis, but the underlying mechanisms are still unclear. So, we conducted this study to explore the effect of miR-126 expression on angiogenesis in hepatocellular carcinoma (HCC) after transcatheter arterial chemoembolization (TACE). The expression levels of miR-126 and sprouty-related, EVH1 domain containing protein (Spred)1 in surgically resected HCC tissue, HCC tissue with TACE + operation, and tumor-adjacent tissues were determined by quantitative real-time polymerase chain reaction. The expression levels of miR-126, Spred1, and vascular endothelial growth factor were found by quantitative real-time polymerase chain reaction and Western blot. The microvessel density (MVD) of tumor tissues was determined by immunohistochemical staining. The miR-126 and Spred1 expressions in HCC tissue with TACE + operation were elevated and decreased, respectively, as compared to those in surgically resected HCC tissues and tumor-adjacent tissues (all P<0.001), which indicated that the expression of Spred1 was negatively correlated with miR-126 (P<0.001, r=-0.6224). Based on the bioinformatics analysis and luciferase reporter gene activity detection, Spred1 was found to target miR-126 (P<0.001). Inhibition of miR-126 expression reduces the degree of weight loss and tumor size in TACE model rats. The MVD in TACE + operation group was increased compared to that in the control group; inhibition of miR-126 expression had a reversal effect, to a certain extent, on MVD increase after TACE (all P<0.05). Inhibition of miR-126 expression increased Spred1 expression and decreased vascular endothelial growth factor expression (P<0.01). In summary, this study unveiled the potential mechanism by which miR-126 regulates angiogenesis in HCC tissues through embolization treatment by targeting Spred1, and also showed that the feasibility of TACE with the miR-126 inhibitor has a certain value in the medical treatment of HCC.

Keywords: microRNA-126, sprouty-related, EVH1 domain containing protein 1, hepatocellular carcinoma, transcatheter hepatic arterial chemoembolization, animal modeling, angiogenesis, vascular endothelial growth factor, microvessel density

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]