Defective expression of polarity protein Par3 promotes cervical tumorigenesis and metastasis

Objectives: The aim of this study was to investigate whether the partition-defective 3 protein (Par3) regulates cervical carcinoma growth and metastasis. Materials and Methods: Immunohistochemistry (IHC) was used to analyze the expression of Par3 protein in samples from 89 cervical squamous cell carcinoma (CSCC) pa tients among Uyghur women. The specific short hairpin (shRNA) vector as well as eukaryotic expression vector of PARD3 was transfected into SiHa cell lines. The variation of migration and invasion after transfection was determined using Transwell assays, cell cycle, and apoptosis were assayed by flow cytometry, respectively. Results: The incidence of CSCC was associated with reduced expression of Par3. Downregulation of Par3 was significantly associated with more advanced tumors (i.e., higher histological grade, lymph node involvement, and higher tumor stages) (p < 0.05 for all). Lost expression of Par3 promotes proliferation, inhibits apoptosis, and enhances migration and invasion. Loss of Par3 induces MMP9 expression and epithelial to mesenchymal transition (EMT) related genes (N-cadherin, E-cadherin, and β-catenin) expression changed in SiHa cells. Conclusions: The reduced Par3 expression in cervical cancer indicates tumor-suppressive properties of Par3 that may be a marker of poor prognosis in cervical cancer patients, and the molecular determinants of epithelial polarity which have tumorigenesis enhancing impact, might through EMT.

Par3 protein; Cervical cancer; Epithelio-mesenchymal transition; MMP9; RNAi.

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