Oncotarget

Research Papers:

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

Zun-yi Zhang _, Sheng-ling Fu, Su-qin Xu, Xiao Zhou, Xian-shen Liu, Yong-jian Xu, Jian-ping Zhao and Shuang Wei

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Oncotarget. 2015; 6:1462-1477. https://doi.org/10.18632/oncotarget.2808

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Abstract

Zun-yi Zhang1, Sheng-ling Fu1, Su-qin Xu2, Xiao Zhou2, Xian-shen Liu2, Yong-jian Xu2, Jian-ping Zhao2, Shuang Wei2

1Department of Surgery, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology, Wuhan 430030, China

2Department 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 p21CIP1/WAF1 expression. These findings reveal that hsa-miR-526b is a potential target in cancer therapy.


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