Overexpression of miRNA-497 inhibits tumor angiogenesis by targeting VEGFR2.
Recent studies reported miR-497 exhibited inhibitory effects in various cancers. However, whether miR-497 is involved in inhibiting angiogenesis, which is critical for tumor growth and metastasis, is still unknown. The purpose of this study was to investigate the potential role of miR-497 in tumor angiogenesis. In this work, cell proliferation and apoptosis analyses were conducted to explore the potential function of miR-497 in HUVECs by using MTT and TUNEL assays. Western blotting (WB) was employed to validate the downstream targets of miR-497. Furthermore, in order to disclose the role of miR-497 on angiogenesis, VEGFR2-luc transgenic mice were treated with miR-497 mimic and applied to monitor tumor angiogenesis and growth by in vivo bioluminescent imaging (BLI). The results demonstrated that overexpression of miR-497 showed inhibitory effects on VEGFR2 activation and downstream Raf/MEK/ERK signal pathways in vitro and in vivo. Moreover, overexpression of miR-497 effectively induced HUVECs apoptosis by targeting VEGFR2 and downstream PI3K/AKT signaling pathway. Furthermore, miR-497 exhibited anti-angiogenesis and anti-tumor effects in the VEGFR2-luc breast tumor model proven by BLI, WB and immunohistochemistry analysis. In summary, miR-497 inhibits tumor angiogenesis and growth via targeting VEGFR2, indicating miR-497 can be explored as a potential drug candidate for cancer therapy.
Key Laboratory of Molecular Imaging, College of Heilongjiang Province, Harbin, Heilongjiang, China.|Department of Cardiology, the Fourth Hospital of Harbin Medical University, Harbin, Heilongjiang, China.|Molecular Imaging Program at Stanford, Department of Radiology and Bio-X Program, Stanford University, Stanford, California, USA.
Yingfeng
Y
Tu
Department of Anesthesiology, the Third Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
Li
L
Liu
Key Laboratory of Molecular Imaging, College of Heilongjiang Province, Harbin, Heilongjiang, China.|Department of Radiology, the Fourth Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
Dongliang
D
Zhao
Department of Cardiology, the Second Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
Youbin
Y
Liu
Molecular Imaging Program at Stanford, Department of Radiology and Bio-X Program, Stanford University, Stanford, California, USA.
Xiaowei
X
Ma
College of Pharmacy, Harbin Medical University, Daqing, Heilongjiang, China.
Yuhua
Y
Fan
Key Laboratory of Molecular Imaging, College of Heilongjiang Province, Harbin, Heilongjiang, China.|Department of Radiology, the Fourth Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
Lin
L
Wan
Key Laboratory of Molecular Imaging, College of Heilongjiang Province, Harbin, Heilongjiang, China.|Department of Radiology, the Fourth Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
Tao
T
Huang
Molecular Imaging Program at Stanford, Department of Radiology and Bio-X Program, Stanford University, Stanford, California, USA.
Zhen
Z
Cheng
Key Laboratory of Molecular Imaging, College of Heilongjiang Province, Harbin, Heilongjiang, China.|Department of Radiology, the Fourth Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
Baozhong
B
Shen
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D015870:Gene Expression; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D020935:MAP Kinase Signaling System; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics* / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays; D048490:raf Kinases / Q000378:metabolism
C559640:MIRN497 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D040301:Vascular Endothelial Growth Factor Receptor-2; D048490:raf Kinases