miR-874 functions as a tumor suppressor by inhibiting angiogenesis through STAT3/VEGF-A pathway in gastric cancer

Abstract

// Xiaoyu Zhang 1, 2, * , Jie Tang 1, * , Xiaofei Zhi 1, * , Kunling Xie 1 , Weizhi Wang 1 , Zheng Li 1 , Yi Zhu 1 , Li Yang 1 , Hao Xu 1 , Zekuan Xu 1 1 Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China 2 Division 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 Correspondence to: Zekuan Xu, e-mail: xuzekuan@njmu.edu.cn Hao Xu, e-mail: brightmoon_1@sina.com Keywords: microRNA-874, tumor angiogenesis, STAT3, VEGF-A, gastric cancer Received: July 27, 2014      Accepted: November 11, 2014      Published: January 22, 2015 ABSTRACT 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.