circPHIP promotes oral squamous cell carcinoma progression by sponging miR-142-5p and regulating PHIP and ACTN4...

Circular RNA (circRNA) is a newly discovered class of noncoding RNAs that plays key regulatory role in pathological development, including the regulation of several solid tumors. However, the effects of circRNA expression on oral squamous cell carcinoma (OSCC) remain unclear. With the use of high-throughput RNA sequencing data on eight paired oral cancer and adjacent healthy tissues, we observed that circRNA derived from the gene encoding pleckstrin homology domain-interacting protein (circPHIP) was highly expressed in OSCC. Additionally, circPHIP was highly expressed in other OSCC-related cell lines and was associated with tumor metastasis, TNM stage, and human papilloma virus infection status. The inhibition of circPHIP expression reduced OSCC cell migration, invasion, and proliferation. We found that circPHIP could adsorb microRNA (miR)-142-5p and upregulate the expression of PHIP and alpha-actinin 4 (ACTN4), both of which are potential oncogenes closely related to OSCC prognosis. The inhibition of miR-142-5p or overexpressing PHIP or ACTN4 reversed the circPHIP depletion-induced attenuation of OSCC malignancy. In conclusion, circPHIP is overexpressed in OSCC and enhances its malignancy via an miR-142-5p/PHIP-ACTN4/AKT serine/threonine kinase 1 signaling axis. Therefore, circPHIP may represent a novel target for treating OSCC.