LncRna CPS1-IT1 Suppresses Cell Proliferation, Invasion and Metastasis in Colorectal Cancer

Cell Physiol Biochem. 2017;44(2):567-580. doi: 10.1159/000485091. Epub 2017 Nov 17.

Abstract

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.

Keywords: CPS1 intronic transcript 1 (CPS1-IT1); Colorectal carcinoma (CRC); Long non-coding RNAs (lncRNAs); Metastasis.

MeSH terms

  • Animals
  • Apoptosis
  • Cell Cycle Checkpoints
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Colorectal Neoplasms / drug therapy
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology*
  • Epithelial-Mesenchymal Transition
  • HCT116 Cells
  • HT29 Cells
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Kaplan-Meier Estimate
  • Liver Neoplasms / pathology
  • Liver Neoplasms / secondary
  • Lung Neoplasms / pathology
  • Lung Neoplasms / secondary
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • RNA Interference
  • RNA, Long Noncoding / antagonists & inhibitors
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • RNA, Small Interfering / metabolism
  • RNA, Small Interfering / therapeutic use
  • Transplantation, Heterologous

Substances

  • RNA, Long Noncoding
  • RNA, Small Interfering