29034

CPS1-IT1

Recently, increasing numbers of long noncoding RNAs (lncRNAs), with both oncogenic and tumor-suppressive potential, have been found to be aberrantly expressed in various human cancers. However, the function of lncRNAs in hepatocellular carcinoma (HCC) progression remains largely unknown. In this study, we performed a comprehensive microarray analysis of lncRNA expression using human HCC specimens. After validation in 119 human HCC tissues, we identified a novel tumor suppressor lncRNA, CPS1 intronic transcript 1 (CPS1-IT1). To elucidate the clinical significance of CPS1-IT1 in HCC, correlations between CPS1-IT1 levels, clinical parameters, and survival outcomes were analyzed. In vitro and in vivo functional assays were also performed to dissect the potential underlying mechanisms. expression of CPS1-IT1 was significantly decreased in 73% of HCC tissues, and patients with low CPS1-IT1 expression had poor survival outcomes. Furthermore, in vitro functional assays indicated that CPS1-IT1 significantly reduced cell proliferation, migration and invasion capacities through reduced Hsp90 binding to and activation of HIF-1alpha, thereby suppressing the epithelial-mesenchymal transition (EMT). An in vivo animal model also demonstrated the tumor suppressor role of CPS1- IT1 via decreased tumor growth and metastasis. In conclusion, lncRNA CPS1-IT1 acts as a tumor suppressor in HCC by reducing HIF-1alpha activation and suppressing EMT. The findings of this study establish a function for CPS1-IT1 in HCC progression and suggest its potential as a new prognostic biomarker and target for HCC therapy.

BACKGROUND/AIMS: Increasing evidence demonstrates that long non-coding RNAs (lncRNAs) regulate diverse cellular processes and cancer progression. Whether lncRNAs play any functional role in colorectal carcinoma (CRC) remains largely unknown. The aim of this study was to investigate the role of lncRNA CPS1 intronic transcript 1 (CPS1-IT1) in CRC. METHODS: expression of CPS1-IT1 was initially assessed in human CRC tissues and in a series of CRC cell lines. The correlations between CPS1-IT1 levels and survival outcomes were analyzed to elucidate the clinical significance of CPS1-IT1 in CRC. The underlying mechanisms of CPS1-IT1 in CRC were analyzed through in vitro and in vivo functional assays. RESULTS: expression of CPS1-IT1 was significantly decreased in CRC tissues and cell lines, and patients with low CPS1-IT1 expression had poor survival outcomes. The results of in vitro assays revealed that CPS1-IT1 significantly reduced cell proliferation, migration and invasion capacities and accelerated cell apoptosis, thereby suppressing epithelial-mesenchymal transition (EMT). An in vivo animal model also demonstrated the tumor-suppressive role of CPS1-IT1. CONCLUSION: In this study, we found that CPS1-IT1 has a tumor-suppressive role in CRC. Our data suggest that CPS1-IT1 could be used as a new prognostic biomarker and therapeutic target for CRC.CI - (c) 2017 The Author(s). Published by S. Karger AG, Basel.