The oncogenic role of circPVT1 in head and neck squamous cell carcinoma is mediated through the mutant p53/YAP/TEAD complex

Background: circular RNAs are a class of endogenous RNAs with various functions in eukaryotic cells. Worthy of note, circular RNAs play a critical role in cancer. Currently, nothing is known about the role of circular RNAs in head and neck squamous cell carcinoma (HNSCC). The identification of circular RNAs in HNSCC might become useful for diagnostic and therapeutic strategies in HNSCC. Results: Using samples from 115 HNSCC patients, we find that circPVT1 is over-expressed in tumors compared to matched non-tumoral tissues, with particular enrichment in patients with TP53 mutations. The circPVT1 up- and down-regulation determine, respectively, an increase and a reduction of the malignant phenotype in HNSCC cell lines. We show that circPVT1 expression is transcriptionally enhanced by the mut-p53/YAP/TEAD complex. CircPVT1 acts as an oncogene modulating the expression of miR-497-5p and genes involved in the control of cell proliferation. Conclusions: This study shows the oncogenic role of circPVT1 in HNSCC, extending the current knowledge about the role of circular RNAs in cancer. We show here Affymetrix profiling of 23 normal and 24 tumor tissues. To select miRNA-497-5p targets, we performed a correlation analysis between miRNA-497-5p expression [1] and mRNA expression analysis of 14 patients with TP53 mutations and 9 normal matched patients. [1] Ganci F, Sacconi A, Bossel Ben-Moshe N, Manciocco V, Sperduti I, Strigari L, et al. Expression of TP53 mutation-associated microRNAs predicts clinical outcome in head and neck squamous cell carcinoma patients. Ann Oncol. 2013;24:3082-088.