Oncotarget

Research Papers:

Let7c inhibits migration and epithelial–mesenchymal transition in head and neck squamous cell carcinoma by targeting IGF1R and HMGA2

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Oncotarget. 2018; 9:8927-8940. https://doi.org/10.18632/oncotarget.23826

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Bo Hou1,2, Hajime Ishinaga1, Kaoru Midorikawa2, Satoshi Nakamura1, Yusuke Hiraku2, Shinji Oikawa2, Ning Ma3, Kazuhiko Takeuchi1 and Mariko Murata2

1Department of Otolaryngology-Head and Neck Surgery, Graduate School of Medicine, Mie University, Tsu, Mie 514-8507, Japan

2Department of Environmental and Molecular Medicine, Graduate School of Medicine, Mie University, Tsu, Mie 514-8507, Japan

3Graduate School of Health Science, Suzuka University of Medical Science, Suzuka, Mie 513-8670, Japan

Correspondence to:

Kazuhiko Takeuchi, email: [email protected]

Mariko Murata, email: [email protected]

Keywords: Let-7c; IGF1R; HMGA2; epithelial–mesenchymal transition; head and neck squamous cell carcinoma

Received: May 02, 2017     Accepted: December 27, 2017     Published: January 02, 2018

ABSTRACT

To elucidate the molecular mechanisms underlying the progression of head and neck squamous cell carcinoma (HNSCC), we investigated the function of let-7c as a tumor suppressor. Let-7c expression was significantly down-regulated in HNSCC tumor tissues and cell lines. In vitro and in vivo studies revealed that let-7c negatively regulated HNSCC proliferation, migration and epithelial–mesenchymal transition (EMT). To explore the underlying mechanisms that affect these molecular events achieved by let-7c, we predicted its target genes. We performed luciferase assay and confirmed that insulin-like growth factor 1 receptor (IGF1R) and high mobility group AT-hook 2 (HMGA2) were the direct targets of let-7c. Knocking down of IGF1R and HMGA2 inhibited HNSCC progression, including proliferation, migration and EMT in HNSCC cells. Re-expression of these genes overcame let-7c-mediated inhibition. Taken together, our finding suggests that let-7c inhibits HNSCC progression by targeting IGF1R and HMGA2 and might be a novel target for HNSCC treatment.