PPIA enhances cell growth and metastasis through CD147 in oral cancer

Abstract

Oral cancer is a malignant tumor, and the associated death rate has significantly increased over the past few decades. Secreted fractions are involved in various physiological processes, and their analysis has become a promising approach for discovering diagnostic and prognostic biomarkers for cancer detection and monitoring metastasis. Therefore, the discovery of potential prognostic, diagnostic, and therapeutic biomarkers for oral cancer metastasis is beneficial for developing effective strategies in oral cancer therapy. In this study, we used secretomic analysis to identify the secreted proteins involved in oral cancer. One of the identified proteins, peptidylprolyl isomerase A (PPIA), was selected for further investigation. We used RNA interference to investigate the effect of PPIA secretion on invasion and migration of OC3–I5 cells. Our results showed that reducing the expression and secretion of PPIA significantly decreased invasion and migration of OC3–I5 cells. Next, we used recombinant PPIA to investigate its direct effect on OC3 cell metastasis. The results revealed that proliferation, migration, and invasion of OC3 cells were significantly increased by treatment with the recombinant PPIA. Immunohistochemical analyses revealed higher PPIA expression in tumor tissues compared to normal tissues. Concisely, PPIA activated the ERK1/2 and p38 MAPK signaling pathways and enhanced cell proliferation and metastasis through CD147. In summary, PPIA may prove to be a novel target for oral cancer therapy as well as a prognostic marker.