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Onco Targets Ther. 2016 Jul 19;9:4357-67. doi: 10.2147/OTT.S106513. eCollection 2016.

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

OncoTargets and therapy

Jian-Song Ji, Min Xu, Jing-Jing Song, Zhong-Wei Zhao, Min-Jiang Chen, Wei-Qian Chen, Jian-Fei Tu, Xiao-Ming Yang

Affiliations

  1. Department 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; Department of Radiology, Lab-Yang, University of Washington, Seattle, WA, USA.
  2. Department 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.
  3. Department of Radiology, Lab-Yang, University of Washington, Seattle, WA, USA.

PMID: 27499630 PMCID: PMC4959414 DOI: 10.2147/OTT.S106513

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

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