miR-551a and miR-551b-3p target GLIPR2 and promote tumor growth in high-risk head and neck cancer by modulating autophagy

Abstract

The potential role for microRNA (miRNA) in the metastatic process that occurs in head and neck squamous cell carcinoma (HNSCC) was examined. miRNA was extracted from surgically excised tumor samples from 41 HNSCC cancer patients diagnosed with distant metastasis (DM) and from 53 patients who displayed no evidence of disease (NED) for a minimum of two years a minimum of two years after treatment with post-operative radiotherapy (PORT). A comparative two-way ANOVA of miRNA expression between DM and NED specimens identified 28 differentially expressed miRNAs with a false discovery rate (FDR) < 0.2 and fold change > 1.5. Two miRNA, miR-551a and miR-551b-3p, which share the same seed sequence, were associated with the DM group and with poor survival. Cell proliferation, migration, and invasion assays using the HN5 and UMSCC-17B HNSCC cell lines were performed after transfecting mimics or inhibitors of these miRNA uncovered an oncogenic role for miR-551a and miR-551b-3p. Furthermore, it was determined that miR-551a and miR-551b-3p directly target GLIPR2 mRNA, a negative regulator of autophagy. Overexpression of GLIPR2 reduced proliferation, migration and invasion of HNSCC cells. In addition, overexpression of miR-551a and miR-551b-3p increased radioresistance while GLIPR2 overexpression increased the radiosensitivity of HNSCC cell lines. These results propose that the miR-551a, miR-551b-3p and GLIPR2 axis plays an important role in tumor growth, invasion and metastasis, at least in part by modulating autophagy and that the proliferative and pro-survival roles of miR-551a and miR-551b-3p may represent potential therapeutic targets by inhibiting autophagy through the regulation of GLIPR2 expression in HNSCC.