Programmed Cell Death 4 is a Direct Target of miR-21 and Regulates Invasion in Oral Squamous Cell Carcinoma

Programmed Cell Death 4 (PDCD4) is a known tumour suppressor, lost in carcinomas of the breast, prostate, colon, lung and ovary. This study found significantly reduced levels of PDCD4 mRNA and protein in both primary patient oral squamous cell carcinomas (OSCCs) and OSCC cell lines. Moreover, lower PDCD4 mRNA levels were significantly correlated with nodal metastasis (P=0.019). To determine the functional significance of PDCD4 down-regulation in OSCC we asked whether PDCD4 played a role in invasion. In fact, over-expression of PDCD4 decreased invasion of OSCC lines. We then sought to determine a mechanism for PDCD4 down-regulation in OSCC. Previous studies in breast and colon carcinomas suggested that reduced PDCD4 expression was due to over-expression of miR-21. Interestingly, miR-21 was inversely correlated to PDCD4 mRNA (P=0.002) and PDCD4 protein (P