OncoTargets and Therapy (Jul 2016)
Inhibition of microRNA-126 promotes the expression of Spred1 to inhibit angiogenesis in hepatocellular carcinoma after transcatheter arterial chemoembolization: in vivo study
Abstract
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
