Increased urothelial cancer associated 1 is associated with tumor proliferation and metastasis and predicts poor prognosis in colorectal cancer

Int J Oncol. 2015 Oct;47(4):1329-38. doi: 10.3892/ijo.2015.3109. Epub 2015 Jul 29.

Abstract

Long non-coding RNA, urothelial cancer associated 1 (UCA1), is reported to play a critical role in progression of carcinogenesis. In the present study, we identified differential expression of UCA1 in colorectal cancer (CRC) and paired peritumoral tissues using gene expression microarray analyses. qPCR analysis confirmed that UCA1 was upregulated in CRC (p<0.001) and the expression of UCA1 was statistically correlated with lymph node metastasis (P=0.040), distant metastasis (P=0.043) and tumor stage (P=0.010). Kaplan-Meier analysis indicated that patients with high UCA1 expression had a poor prognosis. Moreover, multivariate analysis identified UCA1 overexpression as an independent predictor for CRC. We also found that knockdown of UCA1 significantly suppressed cell proliferation and metastasis in CRC cells. Flow cytometry assays showed UCA1 silencing induced G0/G1 growth arrest and apoptosis of CRC cells. To further investigate the regulatory mechanisms of UCA1, we identified that Ets-2 bound to the UCA1 core promoter using luciferase assays. Collectively, our findings suggested that UCA1 might be an important prognostic indicator in CRC and may be a potential target for diagnosis and gene therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / genetics
  • Biomarkers, Tumor / analysis*
  • Cell Proliferation / genetics
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology*
  • Female
  • Flow Cytometry
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Mutagenesis, Site-Directed
  • Neoplasm Invasiveness / genetics
  • Oligonucleotide Array Sequence Analysis
  • Polymerase Chain Reaction
  • Prognosis
  • Proportional Hazards Models
  • RNA, Long Noncoding / analysis
  • RNA, Long Noncoding / biosynthesis*
  • RNA, Small Interfering
  • Transfection

Substances

  • Biomarkers, Tumor
  • RNA, Long Noncoding
  • RNA, Small Interfering
  • UCA1 RNA, human