Microarray analysis of circular RNA expression profiles associated with gemcitabine resistance in pancreatic cancer cells

Oncol Rep. 2018 Jul;40(1):395-404. doi: 10.3892/or.2018.6450. Epub 2018 May 17.

Abstract

Pancreatic cancer (PC) is one of the most malignant tumors of the digestive system due to its rapid progression, metastasis and resistance to chemotherapy. Gemcitabine (GEM) chemotherapy is the first‑choice treatment for advanced PC. However, the effect of GEM‑based chemotherapy on PC is limited due to the development of chemoresistance, and the molecular mechanisms underlying this resistance have yet to be investigated. Circular RNAs (circRNAs), which can function as microRNA sponges, have been found to be involved in the development of several types of cancer. However, research on circRNAs in PC drug resistance is limited. In the present study, the GEM‑resistant PC cell line, SWl990/GZ, was successfully established by treating parental SWl990 cells in vitro with increasing concentrations of GEM in culture medium intermittently for 10 months. By analyzing the expression profiles of circRNAs in microarray between SWl990/GZ and parental SW1990 cells, we identified 26 upregulated and 55 downregulated circRNAs (fold change ≥2 and P<0.05) among 12,866 detected circRNAs in SWl990/GZ compared with SW1990 cells. Furthermore, the changes in the expression of six representative circRNAs was validated by reverse transcription‑quantitative PCR. In addition, Kyoto Encyclopedia of Genes and Genomes pathway analysis and Gene Ontology analysis were performed. These analyses revealed that the dysregulated circRNAs regulated several cancer‑related pathways, such as the mitogen‑activated protein kinase (MAPK) and mammalian target of rapamycin (mTOR) signaling pathways, and may be involved in the biological process of the regulation of chemoresistance, including nucleic acid metabolic process and cellular response to stress. The present study undertook a comprehensive expression analysis and revealed the functional profiles of differentially expressed circRNAs associated with GEM‑resistance in PC, thereby indicating the possible participation of these dysregulated circRNAs in the development of chemoresistance and providing novel potential therapeutic targets for PC.

MeSH terms

  • Cell Line, Tumor
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / adverse effects
  • Deoxycytidine / analogs & derivatives*
  • Drug Resistance, Neoplasm / drug effects*
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Ontology
  • Humans
  • Microarray Analysis
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / pathology
  • RNA / genetics*
  • RNA, Circular
  • RNA, Messenger / genetics
  • Signal Transduction / drug effects

Substances

  • RNA, Circular
  • RNA, Messenger
  • Deoxycytidine
  • RNA
  • gemcitabine