miR-1 as a tumor suppressive microRNA targeting TAGLN2 in head and neck squamous cell carcinoma

Abstract

Nijiro Nohata 1,2,* , Yaeko Sone 1,3,* , Toyoyuki Hanazawa 2 , Miki Fuse 1 , Naoko Kikkawa 1,2 , Hirofumi Yoshino 4 , Takeshi Chiyomaru 4 , Kazumori Kawakami 4 , Hideki Enokida 4 , Masayuki Nakagawa 4 , Makio Shozu 3 , Yoshitaka Okamoto 2 ,and Naohiko Seki 1 1 Department of Functional Genomics, Chiba University Graduate School of Medicine, Chiba, Japan 2 Department of Otorhinolaryngology/Head and Neck Surgery, Chiba University Graduate School of Medicine, Chiba, Japan 3 Department of Gynecologic Oncology, Chiba University Graduate School of Medicine, Chiba, Japan 4 Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan * These authors contributed equally to this work. Keywords: microRNA, miR-1, TAGLN2, tumor suppressor, HNSCC, microarray, oncogenes, oncotargets Received: December 20, 2010; Accepted: January 23, 2011; Published: January 25, 2011; Correspondence: Nijiro Nohata, e-mail: // // Abstract Based on the microRNA (miRNA) expression signatures of hypopharyngeal and esophageal squamous cell carcinoma, we found that miR-1 was significantly down-regulated in cancer cells. In this study, we investigated the functional significance of miR-1 in head and neck squamous cell carcinoma (HNSCC) cells and identified miR-1-regulated novel cancer pathways. Gain-of-function studies using miR-1 revealed significant decreases in HNSCC cell proliferation, invasion, and migration. In addition, the promotion of cell apoptosis and cell cycle arrest was demonstrated following miR-1e transfection of cancer cells. A search for the targets of miR-1 revealed that transgelin 2 (TAGLN2) was directly regulated by miR-1. Silencing of TAGLN2 significantly inhibited cell proliferation and invasion in HNSCC cells. Down-regulation of miR-1 and up-regulation of TAGLN2 were confirmed in HNSCC clinical specimens. Our data indicate that TAGLN2 may have an oncogenic function and may be regulated by miR-1, a tumor suppressive miRNA in HNSCC. The identification of novel miR-1-regulated cancer pathways could provide new insights into potential molecular mechanisms of HNSCC carcinogenesis.