Upregulation of GRIM-19 suppresses the growth of oral squamous cell carcinoma in vitro and in vivo.

Abstract

Constitutive activation of the signal transducer and activator of transcription3 (STAT3) and its upregulation contribute to the progression and metastasis of several different tumor types. The gene associated with retinoid‑interferon‑induced mortality-19 (GRIM-19) is known to functionally interact with STAT3 and inhibit its transcriptional activity. It has been reported that upregulation of genes associated with GRIM-19 can significantly reduce the tumor growth of several types of tumors. However, little is known in regards to its role in oral squamous cell carcinoma (OSCC). In the present study, a recombinant eukaryotic expression plasmid carrying GRIM-19 was constructed to evaluate its effects on OSCC cancer growth. Upregulation of GRIM-19 in OSCC cells significantly inhibited cell proliferation, migration and invasion invitro and suppressed tumor growth invivo. Moreover, we found that upregulation of GRIM-19 reduced cyclin D1, Bcl-2, vascular endothelial growth factor (VEGF) and matrix metalloproteinase-2 (MMP-2) expression whose protein is involved in STAT3 activation. Taken together, these findings suggest that GRIM-19 plays an inhibitory role in the progression of OSCC, and contribute to the future development of STAT3-based gene therapeutic approaches for OSCC.