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Aim:To investigate the effect of the growth arrest-and DNA damage-inducible Gadd45a gene on the radiosensitivity of human tongue squamous cell carcinoma cell line to ionizing radiation (IR). Methods: Short interfering ribonucleic acid (si-RNA) targeting Gadd45a or an irrelevant mRNA (nonsense si-RNA) was chemically synthesized. The constructed si-RNAs were transfected into Tca8113 cells and Gadd45a expression was determined using quantitative real-time PCR and Western-blot. After 24-h exposure to IR at a dose rate of 4 Gy/min, apoptosis of Tca8113 cells was detected using flow cytometry, and radiosensitivity was measured using MTT assays. Results: IR apparently increased the expression of Gadd45a at mRNA and protein levels in Tca8113 cells. The effect was efficiently inhibited by transfection with Gadd45a si-RNA (P<0.01). Furthermore, silencing Gadd45a gene significantly increased cell viability and decreased the percentage of apoptotic cells during irradiation, which indicated that IR-induced Gadd45a over-expression could increase the radiosensitivity of Tca8113 cells. Conclusion: These results indicated that targeting Gadd45a may have important therapeutic implications in sensitizing Tca8113 cells to IR.

The results showed that Gadd45a was redistributed to cytoplasm in poorly differentiated carcinoma from its nucleus location in normal tissue (P < 0.05). The expression of Gadd45a was significantly associated with lymph node metastasis, tumor stage and tumor histological grade (P < 0.05). Knockdown of Gadd45a gene abolished the G2/M arrest and increased migrating ability of Tca8113 cell (P < 0.05). The results indicate that Gadd45a play an important role in OSCC metastasis by affecting the bioactivity of the tumor cells, and its distribution may serve for the prediction of clinical outcome of OSCC.

Our data support that Kif2a is a potential molecular target for the therapeutics of recurrent and metastatic SCCOT.

Oral lichen planus is a chronic inflammatory disorder of the oral mucosa that represents T cell-mediated autoimmune diseases. The regulation and roles of carcinoembryonic antigen-related cellular adhesion molecule 1 (CEACAM1), a novel immune molecule, in the immunopathogenesis of T cell-mediated autoimmune diseases remain unclear. In the current paper, CEACAM1 was found to be overexpressed in peripheral T cells and epithelial cells in oral lichen planus patients. A fraction of infiltrating inflammatory mononuclear cells in the lamina propria of the oral lichen planus mucosa also expressed CEACAM1. Importantly, for the first time, CEACAM1 expression in T cells and in normal human oral keratinocytes was demonstrated to be regulated differently by osteopontin in vitro. Furthermore, the apoptosis of oral keratinocytes and activated T cells can be markedly suppressed by CEACAM1-specific monoclonal antibodies. In conclusion, OPN-regulated CEACAM1 expression may play a critical role in the immunopathogenesis of oral lichen planus.

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