Abstract

BackgroundSplicing factor SRSF3 is an oncogene and overexpressed in various kinds of cancers, however, the function and mechanism involved in colorectal cancer (CRC) remained unclear. The aim of this study was to explore the relationship between SRSF3 and carcinogenesis and progression of CRC.MethodsThe expression of SRSF3 in CRC tissues was detected by immunohistochemistry. The proliferation and invasion rate was analyzed by CCK-8 assay, colony formation assay, transwell invasion assay and xenograft experiment. The expression of selected genes was detected by western blot or real time PCR.ResultsSRSF3 is overexpressed in CRC tissues and its high expression was associated with CRC differentiation, lymph node invasion and AJCC stage. Upregulation of SRSF3 was also associated with shorter overall survival. Knockdown of SRSF3 in CRC cells activated ArhGAP30/Ace-p53 and decreased cell proliferation, migration and survival; while ectopic expression of SRSF3 attenuated ArhGAP30/Ace-p53 and increases cell proliferation, migration and survival. Targeting SRSF3 in xenograft tumors suppressed tumor progression in vivo.ConclusionsTaken together, our data identify SRSF3 as a regulator for ArhGAP30/Ace-p53 in CRC, and highlight potential prognostic and therapeutic significance of SRSF3 in CRC.

Highlights

  • Splicing factor Ser‐ ine/arginine-rich splicing factor 3 (SRSF3) is an oncogene and overexpressed in various kinds of cancers, the func‐ tion and mechanism involved in colorectal cancer (CRC) remained unclear

  • SRSF3 upregulation is prevalent in CRC and associates with poor prognosis First, by analyzing the expression of SRSF3 in CRC cases from 20 CRC cases and one tissue microarray including 90 CRC cases, we found significant higher levels of SRSF3 protein in CRC tissues than in normal colorectal tissues (p < 0.001, Fig. 1a, b)

  • By comparing different clinicopathological features of 90 CRC cases stratified by SRSF3 expression level, we found SRSF3 upregulation significantly associated with poorer differentiation (p = 0.01), more lymph node invasion (p = 0.01), and advanced AJCC stage (p = 0.01, all comparisons by Fisher’s exact test, Table 1)

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Summary

Introduction

Splicing factor SRSF3 is an oncogene and overexpressed in various kinds of cancers, the func‐ tion and mechanism involved in colorectal cancer (CRC) remained unclear. Colorectal cancer (CRC) is one of the most commonly diagnosed cancer in the world, with over one million new cases every year in the world [1]. SR proteins (serine/arginine-rich proteins), functioning as mRNA-binding proteins and alternative splicing factors, have diverse cellular functions including transcription, translation, RNA export, genomic stability, and miRNA processing [2]. Since SR proteins participate in various cellular processes, their aberrant expression may cause various diseases including cancers [3]. SRSF3 (serine/arginine-rich splicing factor 3), known as SRp20, is one of the most famous SR proteins. SRSF3 is a multifunctional protein, and has been found to be involved in various human diseases, including cancers [4].

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