miR‐134 miR‐134 targets PDCD7 PDCD7 to reduce E‐cadherin expression and enhance oral cancer progression

摘要

Oral squamous cell carcinoma (OSCC) is a common malignancy worldwide. This study clarified the oncogenic role of miR‐134 in OSCC. Reporter assays, using both wild‐type and mutant constructs, confirmed 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. As expected, 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 mice, and reduced E‐cadherin (E‐cad) expression. PDCD7 transactivated E‐cad expression via the GC‐box in the promoter. Moreover, miR‐134 ‐associated cellular transformation and E‐cad downregulation was attenuated by PDCD7. Downregulation of both PDCD7 and E‐cad and high levels miR‐134 expression was observed in OSCC tumor tissues. Activation of the miR‐134‐ PDCD7‐E‐cad pathogenesis cascade occurred early during the human and murine oral carcinogenesis process. In conclusion, the oncogenic effect of miR‐134 in oral carcinoma is mediated by reducing PDCD7 and E‐cad expression.