Abstract
Due to their aggressive behavior, local recurrence and distant metastasis, survival rate of advanced stage of the patients with head and neck squamous cell carcinoma (HNSCC) is very poor. Currently available epidermal growth factor receptor (EGFR)-targeted therapies are not considered curative for HNSCC. Therefore, novel approaches for identification of therapeutic targets in HNSCC are needed. All members of the miRNA-29 family (miR-29a, miR-29b, and miR-29c) were downregulated in HNSCC tissues by analysis of RNA-sequencing based microRNA (miRNA) expression signature. Ectopic expression of mature miRNAs demonstrated that the miR-29 family inhibited cancer cell migration and invasion by HNSCC cell lines. Comprehensive gene expression studies and in silico database analyses were revealed that integrin β1 (ITGB1) was regulated by the miR-29 family in HNSCC cells. Overexpression of ITGB1 was confirmed in HNSCC specimens, and high expression of ITGB1 significantly predicted poor survival in patients with HNSCC (p = 0.00463). Knockdown of ITGB1 significantly inhibited cancer cell migration and invasion through regulating downstream of ITGB1-mediated oncogenic signalling. In conclusion, regulation of the antitumor miR-29 family affected integrin-mediated oncogenic signalling to modulate HNSCC pathogenesis; these molecules may be novel therapeutic targets for HNSCC.
Highlights
Patients with head and neck squamous cell carcinoma (HNSCC) usually have metastatic lesions when the disease is first diagnosed, and the 5-year survival rate is less than 50% [1, 2]
The expression levels of miR-29a, miR-29b, and miR-29c were significantly lower in cancer tissues (n = 22) and HNSCC cell lines (SAS and HSC3) than in normal epithelial tissues (n = 22) (P < 0.0001, P = 0.0003, and P < 0.0001, respectively; Supplementary Figure 1A)
The miR-29 family members were clustered at two different human chromosome loci
Summary
Patients with head and neck squamous cell carcinoma (HNSCC) usually have metastatic lesions when the disease is first diagnosed, and the 5-year survival rate is less than 50% [1, 2]. The epidermal growth factor receptor (EGFR)-targeting monoclonal antibody cetuximab has been approved for the treatment of patients with HNSCC, the curative effects of this drug are limited [3, 4]. The identification of novel molecular targets in metastatic activating pathways would help to develop new therapies for this disease. Accumulating evidence has showed that aberrant expression of miRNAs disrupts systematically controlled RNA networks in cancer cells [7]. These events are deeply involved in cancer progression, metastasis, and drug resistance [8]. We have sequentially identified novel cancer pathways based on antitumor miRNAs in several cancers [9–14]
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