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

FEBS Open Bio

Shi Li¹  Ximian Liao¹  Zesong Li¹  Yanxin Lu¹  Longyi Mao¹  Tongyu Wang¹ 

[1] Guangdong Key Laboratory of Systems Biology and Synthetic Biology for Urogenital Tumors Shenzhen Second People's Hospital First Affiliated Hospital of Shenzhen University China;

关键词: invasion;    migration;    pregnancy‐associated plasma protein A;    proliferation;    renal cell carcinoma;    tumor suppressor;   

DOI  :  10.1002/2211-5463.13156

来源: DOAJ

【 摘 要 】

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‐3β and β‐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.

【 授权许可】

Unknown