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Let-7c inhibits migration and epithelial?mesenchymal transition in head and neck squamous cell carcinoma by targeting IGF1R and HMGA2 #MMPMID29507664
Hou B; Ishinaga H; Midorikawa K; Nakamura S; Hiraku Y; Oikawa S; Ma N; Takeuchi K; Murata M
Oncotarget 2018[Feb]; 9 (10): 8927-40 PMID29507664show ga
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.