The Role And Mechanism Of Ribosomal Protein S15a In Colorectal Cancer

Eukaryotic ribosome is composed of four types of ribosomal RNA(rRNA)molecules and 79 different ribosomal proteins(RPs),of which the primary responsibility is to participate in ribosome formation and protein synthesis.However,RPs have attracted a wide spread attention for their function beyond the ribosome.That is,RPs were found to be implicated in a broad range of physiological and pathological processes,including transcription,translation control,immune signaling,cell cycle progression,apoptosis and tumorigenesis.To date,some RPs have been found to be upregulated in a set of malignancies in terms of mRNA or protein expression,and overexpressed RPs might play an oncogenic role in cancer.The present study aimed to further investigate the role and mechanism of ribosomal protein S15a(RPS15a)in colorectal cancer(CRC).First of all,we evaluated the expression of RPS15 a in CRC and matched para-cancerous tissue,exploring the potential correlation between RPS15 a level and patients' prognosis.Moreover,we subcutaneously transplanted RKO cells with deletion of RPS15 a to nude mice to understand the effect of RPS15 a knockdown on tumorigenesis.Finally,we conducted genechip analysis on RPS15 a deleted RKO cells,detected the impact on gene expression and verified the differentially expressed genes through real-time fluorescent quantitative PCR and Western-blot assay,with the attempt to learn that RPS15 a works in colorectal cancer via influencing which genes expression.The results showed that the disease-free survival rate of 3 years in RPS15 a negaive group(75%,12/16)was significantly better than that in RPS15 a positive group(44.2%,46/104).The Kaplan-Meier survival analysis found that the average disease-free time of patients in RPS15 a negaive group(32 mouths)is significantly longer than that in RPS15 a positive group(25 mouths).Additionally,the formation of transplanted tumor in nude mice was greatly repressed when RPS15 a knockdown.Genechip detection revealed that RPS15 a may play the oncogenic role in colorectal cancer through regulation of BIRC3,RALB and CASP3.These findings implied that the expression level of RPS15 a in colorectal cancer is correlated with the prognosis of patients and RPS15 a may be associated with the development and progression of CRC by acting as tumor promoter.Our results demonstrated that RPS15 a has the potential to serve as a therapeutic target for the treatment of CRC.