| Summary: | 博士 === 國立陽明大學 === 口腔生物研究所 === 106 === Oral squamous cell carcinoma (OSCC) is a common malignancy worldwide. miR-134 is involved in the pathogenesis of many types of malignancies. This study clarified the oncogenic role of miR-134 in OSCC. Reporter assays, using both wild-type and mutant constructs, indicated that Programmed Cell Death 7 (PDCD7) gene was a potential target of miR-134. The OSCC cells exogenously expressed miR-134 exhibited reduced PDCD7 expression. Exogenous miRZip-134 expression increased PDCD7 expression in the OSCC cells; additionally, PDCD7 expression suppressed the oncogenicity of the OSCC cells. By contrast, PDCD7 knockout through gene editing increased in vitro oncogenicity and neck nodal metastasis in NOD-SCID mice, and reduced E-cadherin expression. PDCD7 transactivated E-cadherin expression via the GC-box in the promoter. Moreover, miR-134-associated cellular transformation and E-cadherin downregulation was attenuated by PDCD7. Downregulation of both PDCD7 and E-cadherin and high levels miR-134 expression was observed in OSCC tumors. Activation of the miR-134-PDCD7-E-cadherin pathogenesis cascade occurred early during the human and mouse oral carcinogenesis process. This study concludes that the oncogenic effect of miR-134 in oral carcinoma is mediated by reducing PDCD7 and E-cadherin expression.
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