miR-193a-3p regulation of chemoradiation resistance in oesophageal cancer cells via the PSEN1 gene

Gene. 2016 Apr 1;579(2):139-45. doi: 10.1016/j.gene.2015.12.060. Epub 2015 Dec 29.

Abstract

Chemoradiation therapy is an important component of the curative treatment for oesophageal carcinomas. These therapeutic effects are prevented in patients according to radioresistance and multi-drug resistance, and the cause of such resistance remains unclear. In this study, we identified the role of miR-193a-3p in modulating the radioresistance and chemoresistance of oesophageal cancer cells. We found that KYSE150 and KYSE410 cells could be characterized as relatively radiation-sensitive and radiation-resistant cells, respectively. Similarly, KYSE150 and KYSE410 cells were found to be chemosensitive and chemoresistant, respectively. Over-expression of miR-193a-3p increased the radioresistance and chemoresistance of oesophageal squamous cell carcinoma (ESCC) cells. In contrast, the down-regulation of miR-193a-3p decreased the radioresistance and chemoresistance of ESCC cells. In addition, miR-193a-3p inducing DNA damage has also been demonstrated through measuring the level of gamma-H2AX associated with miR-193a-3p. Moreover, a small interfering RNA(siRNA)-induced repression of the PSEN1 gene had an effect similar to that of miR-193a-3p up-regulation. The above processes also inhibited oesophageal cancer cells apoptosis. These findings suggest that miR-193a-3p contributes to the radiation and chemotherapy resistance of oesophageal carcinoma by down-regulating PSEN1. Thus, miR-193a-3p and PSEN1 might be potential biomarkers for chemoradiation resistant cancers.

Keywords: ESCC; PSEN1; Radioresistance; X-ray; miR-193a-3p; r-H2AX.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Apoptosis / radiation effects
  • Cell Line, Tumor
  • Chemoradiotherapy
  • DNA Damage / drug effects
  • DNA Damage / radiation effects
  • Drug Resistance, Neoplasm / genetics*
  • Esophageal Neoplasms / drug therapy
  • Esophageal Neoplasms / genetics*
  • Esophageal Neoplasms / radiotherapy
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Expression Regulation, Neoplastic / radiation effects
  • Humans
  • MicroRNAs / biosynthesis
  • MicroRNAs / genetics*
  • Presenilin-1 / biosynthesis*
  • Presenilin-1 / genetics
  • Xenograft Model Antitumor Assays

Substances

  • MIRN193 microRNA, human
  • MicroRNAs
  • PSEN1 protein, human
  • Presenilin-1