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

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

doi:10.18632/oncotarget.23826

Bo Hou, Shinji Oikawa + Show 7 more

Open Access

https://doi.org/10.18632/oncotarget.23826

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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.

Highlights

Head and neck cancer is one of the most common types of human cancer, with nearly 690,000 new cases and 380,000 deaths occurring each year [1]
We found that let-7c expression was significantly decreased in head and neck squamous cell carcinoma (HNSCC) tissues compared to adjacent non-tumor tissues [10]
These results indicate that insulin-like growth factor 1 receptor (IGF1R) and HMGA2 might be involved in HNSCC carcinogenesis through let-7c downregulation

Summary

Introduction

Head and neck cancer is one of the most common types of human cancer, with nearly 690,000 new cases and 380,000 deaths occurring each year [1]. 90% of these tumors are head and neck squamous cell carcinoma (HNSCC) [2]. The therapy for HNSCC usually includes surgery with or without concurrent chemotherapy and radiation therapy, or radiation alone. Despite the use of advanced surgical techniques and effective chemotherapeutic agents, the overall survival of patients with HNSCC has remained unchanged, with a 5-year survival rate of about 50% [3]. Metastasis accounts for the majority of deaths of patients with HNSCC [4]. The molecular mechanisms that promote HNSCC proliferation and migration are largely unknown. There is an urgent need to identify target molecules for novel therapeutic strategies

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