Oncotarget

Research Papers:

Let-7c inhibits migration and epithelial–mesenchymal transition in head and neck squamous cell carcinoma by targeting IGF1R and HMGA2

Bo Hou, Hajime Ishinaga, Kaoru Midorikawa, Satoshi Nakamura, Yusuke Hiraku, Shinji Oikawa, Ning Ma, Kazuhiko Takeuchi _ and Mariko Murata

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

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Abstract

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: kazuhiko@clin.medic.mie-u.ac.jp

Mariko Murata, email: mmurata@doc.medic.mie-u.ac.jp

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.


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