Crm1 knockdown by specific small interfering RNA reduces cell proliferation and induces apoptosis in head and neck cancer cell lines

Abstract

Head and neck squamous cell carcinoma (HNSCC) is the most common and most aggressive type of head and neck cancer. Current approaches for the treatment of HNSCC are not sufficient to increase the patient survival or to reduce the high recurrence rate. Consequently, there is a need to explore the molecular characteristics of this cancer in order to discover potential therapeutic target molecules. The overexpression of chromosome region maintenance 1 (Crm1), responsible for the transport of different classes of macromolecules from the nuclear membrane to the cytoplasm, in various cancer cells has made it an attractive target molecule in cancer research. It has been reported that transcription factors, which are the target cargo proteins of Crm1, have critical roles in regulating intracellular processes via their expression levels and functions, which in turn are regulated by the cell cycle and signaling proteins. Previous findings show that head and neck cancer cells overexpress Crm1 and that these cells become highly dependent on Crm1 function. The results of this study show that after decreasing Crm1 expression levels in HNSCC cells through either treatment with specific Crm1 RNA interference (siRNA) or the selective Crm1 inhibitor leptomycin B (LMB), cell viability, proliferation, migration, and wound-healing abilities decreased, suppressing tumorigenic properties through the induction of apoptosis. Crm1 is a powerful diagnostic biomarker because of its central role in cancerogenesis, and it has a high potential for the development of targeted Crm1 molecules or synthetic agents, such as LMB, as well as for the improvement of the clinical features in head and neck cancer.