K14‐EGFP‐miR‐31 transgenic mice have high susceptibility to chemical‐induced squamous cell tumorigenesis that is associating with Ku80 repression. Issue 6 (6th August 2014)

• Record Type: Journal Article
• Authors: Tseng, Ssu‐Hsueh; Yang, Cheng‐Chieh; Yu, En‐Hao; Chang, Christine; Lee, Yong‐Syu; Liu, Chung‐Ji; Chang, Kuo‐Wei; Lin, Shu‐Chun
• Is Part Of: International journal of cancer. Volume 136:Issue 6(2015:Mar. 15)
• Page Start: 1263
• Page End: 1275
• Publication Date: 2014-08-06
• Subjects: Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.29106
• Languages: English
• ISSNs: 0020-7136

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Squamous cell carcinoma (SCC) occurring in the head and neck region and the esophagus causes tremendous cancer mortality around the world. <italic>miR‐31</italic> is among the most eminently upregulated MicroRNAs in SCC, when it occurs in the head and neck region and the esophagus. We established <italic>miR‐31</italic> transgenic mouse lines, in which <italic>miR‐31</italic> is under the control of the K14 promoter. 4‐nitroquinoline 1‐oxide (4NQO) is a mutagen that causes double strand breaks. The transgenic mice exhibited a higher potential for tumor induction than wild‐type (Wt) mice of the tongue and esophagus after 4NQO treatment. After 4NQO treatment or irradiation, p‐γH2AX expression in squamous epithelium of transgenic mice was increased more than in Wt mice. Exogenous expression of <italic>miR‐31</italic> was also found to be associated with the higher p‐γH2AX expression induced by 4NQO in human oral SCC (OSCC) cell lines. The repair genes PARP1 and Ku80 were validated as new targets of <italic>miR‐31</italic> in human OSCC cell lines, and were found to be downregulated in the squamous epithelium of the tongue in transgenic mice. However, only the downregulation of Ku80 was essential for maintaining the high level of p‐γH2AX induced by 4NQO in OSCC cells. Inverse expression profiles for <italic>miR‐31</italic> and Ku80 were noted in human OSCC tissue. Our study identifies the high sensitivity of <italic>K14‐EGFP‐miR‐31</italic> transgenic mice to chemical carcinogen‐induced squamous cell tumorigenesis and shows that this seems to be associated with the downregulation of Ku80 and an impairment of repair activity in squamous cells, which are mediated by <italic>miR‐31</italic>.</p> </abstract>