By downregulating Ku80, hsa-miR-526b suppresses non-small cell lung cancer

Abstract

// Zun-yi Zhang 1 , Sheng-ling Fu 1 , Su-qin Xu 2 , Xiao Zhou 2 , Xian-shen Liu 2 , Yong-jian Xu 2 , Jian-ping Zhao 2 , Shuang Wei 2 1 Department of Surgery, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology, Wuhan 430030, China 2 Department of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology, Wuhan 430030, China Correspondence to: Shuang Wei, e-mail: wsdavid2001@163.com Keywords: hsa-miR-526b, Ku80, microRNA, NSCLC, p53 Received: August 24, 2014      Accepted: November 24, 2014      Published: December 22, 2014 ABSTRACT Ku80 is involved in DNA double-strand breaks (DSBs) repair. Ku80 is overexpressed in lung cancer tissues, yet, molecular mechanisms have not been examined. We identified that miRNA, hsa-miR-526b, is bound to the 3’-UTR of Ku80 mRNA, thus decreasing Ku80 expression in NSCLC cells. Hsa-miR-526b was downregulated in NSCLC tissues compared with corresponding non-tumorous tissues, and its expression was inversely correlated with Ku80 upregulation. Overexpression of Ku80 and downregulation of hsa-miR-526b were associated with poor clinical outcomes of NSCLC patients. Hsa-miR-526b suppressed NSCLC cell proliferation, clonogenicity, and induced cell cycle arrest and apoptosis. Hsa-miR-526b inhibited xenografts and orthotopic lung tumor growth. Further, Ku80 knockdown in NSCLC cells suppressed tumor properties in vitro and in vivo similar to hsa-miR-526b overexpression. In agreement, Ku80 restoration partially reversed cell cycle arrest and apoptosis induced by hsa-miR-526b in NSCLC cells in vitro and in vivo . In addition, hsa-miR-526b overexpression or Ku80 knockdown increased p53 and p21 CIP1/WAF1 expression. These findings reveal that hsa-miR-526b is a potential target in cancer therapy.