miR-874 functions as a tumor suppressor by inhibiting angiogenesis through STAT3/VEGF-A pathway in gastric cancer
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Xiaoyu Zhang1,2,*, Jie Tang1,*, Xiaofei Zhi1,*, Kunling Xie1, Weizhi Wang1, Zheng Li1, Yi Zhu1, Li Yang1, Hao Xu1, Zekuan Xu1
1Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
2Division of Gastrointestinal Surgery, Department of General Surgery, Huai’an People’s Hospital, Xuzhou Medical College, Huai’an, Jiangsu, China
*These authors have contributed equally to this work
Zekuan Xu, e-mail: [email protected]
Hao Xu, e-mail: [email protected]
Keywords: microRNA-874, tumor angiogenesis, STAT3, VEGF-A, gastric cancer
Received: July 27, 2014 Accepted: November 11, 2014 Published: January 22, 2015
MicroRNAs are endogenously expressed, small non-coding RNAs that regulate gene expression by targeting mRNAs for translational repression or degradation. Our previous studies indicated that miR-874 played a suppressive role in gastric cancer (GC) development and progression. However, the role of miR-874 in tumor angiogenesis and the mechanisms underlying its function in GC remained to be clarified. Here, gain- and loss-of-function assays demonstrated that miR-874 inhibited the tumor angiogenesis of GC cells in vitro and in vivo. Through reporter gene and western blot assays, STAT3 was shown to be a direct target of miR-874. Overexpression of STAT3 rescued the loss of tumor angiogenesis caused by miR-874. Conversely, the STAT3-shRNA attenuated the increased tumor angiogenesis caused by the miR-874-inhibitor. Furthermore, the levels of miR-874 were inversely correlated with those of STAT3 protein in GC tissues. Taken together, these findings indicate that down-regulation of miR-874 contributes to tumor angiogenesis through STAT3 in GC, highlighting the potential of miR-874 as a target for human GC therapy.
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