PAPP‐A functions as a tumor suppressor and is downregulated in renal cell carcinoma

Abstract

Pregnancy-associated plasma protein A (PAPP-A) is a proteolytic enzyme produced by the placenta. The expression and role of PAPP-A in renal cell carcinoma (RCC) remain elusive. The aim of this study was to investigate the role and the molecular mechanisms of PAPP-A in RCC. Initially, we evaluated the expression of PAPP-A in samples from patients with RCC and cell lines by quantitative PCR, western blot and immunohistochemical staining, and examined the role of PAPP-A in RCC cells by cell viability, colony formation and Transwell assays. Next, we investigated the molecular mechanisms regulating the tumor suppressor function of PAPP-A. Our results demonstrated that PAPP-A is expressed at low levels in RCC tissues and cells. Clinical data analysis revealed a significant correlation between PAPP-A expression and RCC-related death (P < 0.0115). Overexpression of PAPP-A inhibited viability, proliferation, migration and invasion of RCC cells. Furthermore, PAPP-A overexpression significantly increased phosphorylation of c-Jun N-terminal kinase and decreased the expression of cyclin D1, phosphorylated glycogen synthase kinase-3b and b-catenin. This study is the first to report that downregulation of PAPP-A is associated with poor prognosis in patients with RCC. In conclusion, PAPP-A may serve as a novel prognostic marker and potentially as a therapeutic target in patients with RCC.Renal cell carcinoma (RCC) comprises 2% to 3% of all adult malignancies; RCC has had a high incidence rate in recent years and accounts for~80% of primary renal malignancies [1]. Clear cell RCC (ccRCC) accounts for about 80% of RCCs and is the most aggressive subtype of RCC. Partial nephrectomy is the most effective therapeutic method for early and local RCC. However, up to 30% of patients experience development of metastases after surgery [2]. The mechanism of RCC formation and progression remains unclear. Therefore, exploring new targets associated with tumorigenesis may improve the potential therapeutic strategies and the therapeutic response of RCC.

The Clinical Relevance and Tumor Promoting Function of C19orf10 in Kidney Renal Clear Cell Carcinoma

“…We detected cell migration and invasion using Transwell assay as described previously ( 14 ). In total, 5×10 4 cells/well in serum-free medium were seeded into the top chamber (pore size, 8 µm; Corning Incorporated, Corning, NY, USA).…”