Epigenetic silencing of miR-130a ameliorates hemangioma by targeting tissue factor pathway inhibitor 2 through FAK/PI3K/Rac1/mdm2 signaling

Gao,Feng; Wang,Fa-Gang; Liu,Ren-Rong; Xue,Feng; Zhang,Jian; Xu,Guang-Qi; Bi,Jian-Hai; Meng,Zhen; Huo,Ran

doi:10.3892/ijo.2017.3943

Epigenetic silencing of miR-130a ameliorates hemangioma by targeting tissue factor pathway inhibitor 2 through FAK/PI3K/Rac1/mdm2 signaling

Authors:
- Feng Gao
- Fa-Gang Wang
- Ren-Rong Liu
- Feng Xue
- Jian Zhang
- Guang-Qi Xu
- Jian-Hai Bi
- Zhen Meng
- Ran Huo
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Affiliations: Department of Aesthetic, Plastic and Burn Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shangdong 250021, P.R. China
Published online on: April 3, 2017 https://doi.org/10.3892/ijo.2017.3943
Pages: 1821-1831

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Abstract

Hemangiomas are the most common vascular tumors that occur frequently in prematures and females. microRNA (miR)-130a is associated with the growth and invasion in many tumors, and its role in hemangiomas has not been addressed so far. The present study revealed that miR‑130a was overexpressed in infantile hemangioma tissues compared with matched tumor-adjacent tissues. The inhibitor of miR-130a restrained cell growth and induced cell apoptosis in vitro. miR‑130a inhibitor also induced a cell cycle arrest at G2/M phase. Further studies revealed that tissue factor pathway inhibitor 2 (TFPI2) was a novel miR-130a target, due to miR-130a bound directly to its 3'-untranslated region and miR-130a inhibitor enhanced the expression of TFPI2. Contrary to the effects of miR-130a inhibitor, TFPI2 siRNA strongly promoted cell growth and colony formation, whereas TFPI2 overexpression contributed to the suppressing effect of miR-130a inhibitor in cell viability. Furthermore, miR-130a inhibitor reduced the activation of focal adhesion kinase (FAK)/phosphoinositide 3-kinase (PI3K)/Rac1/anti-mouse double minute (mdm2) pathway proteins, inhibited the expression and nuclear translocation of mdm2. Moreover, FAK overexpression prevented miR-130a inhibitor-induced cell cycle arrest and decrease of cell viability. In vivo experiments, miR-130a inhibition effectively suppressed the tumor growth, restrained angiogenesis by decreasing the expression of angiogenesis markers and the percentage of CD31+ and CD34+. Taken together, our research indicated that miR-130a functions as an oncogene by targeting TFPI2, miR-130a inhibition reduced the growth and angiogenesis of hemangioma by inactivating the FAK/PI3K/Rac1/mdm2 pathway. Thus, miR-130a may serve as a potential therapeutic strategy for the treatment of hemangioma.

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