期刊
JOURNAL OF CLINICAL MEDICINE
卷 8, 期 4, 页码 -出版社
MDPI
DOI: 10.3390/jcm8040560
关键词
UNR; CSDE1; colorectal cancer; metastasis; prognosis biomarker; c-MYC
资金
- RNA-Reg Consolider-Consortium of the Spanish Ministry of Economy, Industry, and Competitiveness [CSD2009-00080]
- Spanish Health Research Project Funds from Instituto de Salud Carlos III - FEDER of the Spanish Ministry of Economy, Industry, and Competitiveness [PI16/01468]
CSDE1 (cold shock domain containing E1) gene is located upstream of the N-RAS locus, and codes for an RNA-binding protein named Upstream of N-Ras (UNR). In cancer, CSDE1 has been shown to regulate c-Fos, c-Myc, Pten, Rac1, or Vimentin. UNR/CSDE1 has been studied in breast, melanoma, pancreatic and prostate cancer. Then, the aim of this study is to evaluate the role of CSDE1/UNR in colorectal cancer progression and maintenance of aggressive phenotype. We firstly evaluated UNR/CSDE1 expression in human colon cancer derived cell lines and patient samples. Subsequently, we performed functional experiments by UNR/CSDE1 downregulation. We also evaluated UNR/CSDE1 prognostic relevance in two independent sets of patients. Not only was UNR/CSDE1 expression higher in tumor samples compared to untransformed samples, but also in colonospheres and metastatic origin cell lines than their parental and primary cell lines, respectively. Downregulation of UNR/CSDE1 reduced cell viability and migration throughout a restrain of epithelial-to-mesenchymal transition and increases sensitivity to apoptosis. Interestingly, high UNR/CSDE1 expression was associated with poor prognosis and correlated positively with c-MYC expression in colorectal cancer samples and cell lines. Here, we show for the first time compelling data reporting the oncogenic role of UNR/CSDE1 in human colorectal cancer.
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