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

miR-1 作为靶向 TAGLN2 的肿瘤抑制 microRNA 在头颈部鳞状细胞癌中的应用

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作者:Nijiro Nohata, Yaeko Sone, Toyoyuki Hanazawa, Miki Fuse, Naoko Kikkawa, Hirofumi Yoshino, Takeshi Chiyomaru, Kazumori Kawakami, Hideki Enokida, Masayuki Nakagawa, Makio Shozu, Yoshitaka Okamoto, Naohiko Seki

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.

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