Ribosomal protein S15A promotes malignant transformation and predicts poor outcome in colorectal cancer through misregulation of p53 signaling pathway.

Abstract

Ribosomal protein S15A (RPS15A), which has been identified as a highly conserved 40S ribosomal protein, is essential for cell survival and proliferation. The present study evaluated the functional role of RPS15A in colorectal cancer (CRC), and our investigation found that RPS15A was highly expressed in a cohort of human CRC. High RPS15A expression was associated with older age (P=0.035), not receiving preoperative neoadjuvant treatment (P=0.048), higher primary pN stage (P=0.007) and slightly more synchronous distant metastases (P=0.058). The Cox univariate and multivariate hazard regression analysis revealed that higher expression of RPS15A led to a reduction of overall survival rate in CRC, indicating that enhanced RPS15A expression functions as an independent risk factor for the prognosis of CRC patients (P<0.001). Cell based analysis showed that RPS15A was widely expressed in human CRC cell lines. Knockdown of RPS15A significantly suppressed cell proliferation and colony formation in HCT116 and DLD-1 cells, and induced cell cycle arrest at G0/G1 phase. Genechip analysis suggested that knockdown of RPS15A might affect the p53 signaling pathway. Further study indicated that RPS15A knockdown upregulated p53 and p21 expression whereas downregulated CDK1 expression. In summary, the present study identified RPS15A as a novel univariate prognostic factor predicting a poor outcome in CRC patients. The RPS15A overexpression induced by malignant transformation of CRC might function through the p53 signaling pathway.