A long non-coding RNA snaR contributes to 5-fluorouracil resistance in human colon cancer cells

Mol Cells. 2014 Jul;37(7):540-6. doi: 10.14348/molcells.2014.0151. Epub 2014 Jul 31.

Abstract

Several types of genetic and epigenetic regulation have been implicated in the development of drug resistance, one significant challenge for cancer therapy. Although changes in the expression of non-coding RNA are also responsible for drug resistance, the specific identities and roles of them remain to be elucidated. Long non-coding RNAs (lncRNAs) are a type of ncRNA (> 200 nt) that influence the regulation of gene expression in various ways. In this study, we aimed to identify differentially expressed lncRNAs in 5-fluorouracil-resistant colon cancer cells. Using two pairs of 5-FU-resistant cells derived from the human colon cancer cell lines SNU-C4 and SNU-C5, we analyzed the expression of 90 lncRNAs by qPCR-based profiling and found that 19 and 23 lncRNAs were differentially expressed in SNU-C4R and SNU-C5R cells, respectively. We confirmed that snaR and BACE1AS were downregulated in resistant cells. To further investigate the effects of snaR on cell growth, cell viability and cell cycle were analyzed after transfection of siRNAs targeting snaR. Down-regulation of snaR decreased cell death after 5-FU treatment, which indicates that snaR loss decreases in vitro sensitivity to 5-FU. Our results provide an important insight into the involvement of lncRNAs in 5-FU resistance in colon cancer cells.

Keywords: 5-Fluorouracil; cell viability; drug resistance; long non-coding RNAs; snaR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle / drug effects
  • Cell Cycle / immunology
  • Cell Death / drug effects
  • Cell Death / genetics
  • Cell Growth Processes / drug effects
  • Cell Growth Processes / genetics
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cell Survival / genetics
  • Colonic Neoplasms / drug therapy*
  • Colonic Neoplasms / genetics
  • Down-Regulation
  • Drug Resistance, Neoplasm / genetics
  • Fluorouracil / pharmacology*
  • Humans
  • RNA, Long Noncoding / genetics*
  • RNA, Small Interfering / genetics
  • Transcriptome

Substances

  • BACE1-AS long non-coding RNA, human
  • RNA, Long Noncoding
  • RNA, Small Interfering
  • long non-coding RNA snaR, human
  • Fluorouracil