Abstract
MicroRNAs (miRNAs) serve as regulatory factors in both healthy tissue and various cancers. Here, we used an miRNA microarray to screen for miRNAs differentially expressed between HNSCC and adjacent epithelial tissue. Among these, levels of miR-141 were significantly reduced in HNSCC tissues. Expression levels of epidermal growth factor receptor (EGFR) were enhanced in tissues with low miR-141 expression but were reduced by miR-141 overexpression, and there was a significant negative correlation between EGFR and miR-141 levels in HNSCC tissues (P < 0.01). Luciferase assays confirmed that miR-141 targeted EGFR mRNA. In vitro, miR-141 inhibited the proliferation and migration of Cal-27 and FaDu HNSCC cells with corresponding decreases in CDK4 and MMP2. miR-141 also enhanced the incidence of apoptosis among the cells with a corresponding decrease in bcl-2. In BALB/c mice injected with FaDu HNSCC cells, miR-141 mitigated hepatic metastasis and inhibited expression of EGFR, CDK4, bcl-2 and MMP2. These results suggest that miR-141 functions as a tumor suppressor in HNSCC and that it suppresses tumor growth and metastasis by suppressing EGFR signaling. MiR-141 thus appears to be a potentially useful therapeutic target in the treatment of HNSCC.
Highlights
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common type of human cancer, with more than 70% of patients suffering with recurrent or metastatic disease [1]
Further analysis revealed that levels of miR-141 expression are lower in HNSCC tissues than adjacent normal tissues and that the decrease correlated with the occurrence and development of HNSCC (Table 2, Fig. 1A, B)
Consistent with the luciferase activity, we observed that Epidermal growth factor receptor (EGFR) mRNA and protein expression was relatively high, while miR-141 expression was relatively low, in HNSCC cells (Fig. 2C, D)
Summary
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common type of human cancer, with more than 70% of patients suffering with recurrent or metastatic disease [1]. MiRNAs play fundamental roles in normal physiological and pathological processes, including cancer. Epidermal growth factor receptor (EGFR) is a widely distributed cell surface receptor involved in the physiological processes of cell growth and differentiation as well as in cancer metastasis. More than 90% of HNSCCs exhibit upregulated EGFR expression [6, 7]. Identification of key factors that inhibit EGFR expression may improve the treatment of HNSCC. We examined the effects of miR-141 on EGFR expression in HNSCC cells. We analyzed the effects of miR-141 on proliferation, apoptosis and migration of HNSCC cells in vivo and in vitro. Our findings suggest miR-141 acts www.aging-us.com as a tumor suppressor by targeting EGFR expression in HNSCC cells
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