USP7 overexpression predicts a poor prognosis in lung squamous cell carcinoma and large cell carcinoma

• DOI: 10.1007/s13277-014-2773-4
• Publication Date: 2014-12-17T13:47:51Z
• Authors: Guang-Yin Zhao; Zong-Wu Lin; Chun-Lai Lu; Jie Gu; Yun-Feng Yuan; Feng-Kai Xu; Rong-Hua Liu; Di Ge; Jian-Yong Ding
• Keywords: Male; Cancer Research; Epithelial-Mesenchymal Transition; Lung Neoplasms; Down-Regulation; Mice, Nude; Mice; 03 medical and health sciences; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Animals; Humans; Mice, Inbred BALB C; 0303 health sciences; Proto-Oncogene Proteins c-mdm2; Middle Aged; Prognosis; 3. Good health; Lymphatic Metastasis; Carcinoma, Squamous Cell; Carcinoma, Large Cell; Female; Tumor Suppressor Protein p53; Ubiquitin Thiolesterase; Research Article

In non-small cell lung cancer (NSCLC), both USP7 expression and p53 gene status were reported to be an indicator of poor prognosis in adenocarcinoma patients; however, its roles mechanisms squamous carcinoma large need clarified. The was examined NSCLC tumors (excluding adenocarcinoma), their corresponding non-tumorous tissues, cells. Then, the prognostic role analyzed 110 samples adenocarcinoma). Finally, proliferation, metastasis, invasion a assessed using specific vshRNA. higher tissues compared samples, accordingly, high level detected lines with HBE cell. After downregulation, H460 cells exhibited decreased metastasis/invasion vitro vivo. preliminary mechanism study indicated overexpression might regulate p53-MDM2 pathway by inducing MDM2 de-ubiquitination subsequent stabilization, which resulted upregulation Bad phosphorylation. Additionally, we also found that induce epithelial-mesenchymal transition enhance invasive ability. Clinically, significantly correlated malignant phenotype. Furthermore, 5-year overall survival patients USP7(low) than USP7(high). Multivariate analysis showed independent marker for these cancers. may properties cells, serve as molecular target.