Complex role of miR-130a-3p and miR-148a-3p balance on drug resistance and tumor biology in esophageal squamous cell carcinoma

A. K. Eichelmann*, C. Matuszcak, K. Lindner, J. Haier, D. J. Hussey, R. Hummel

*Corresponding author for this work
3 Citations (Scopus)

Abstract

miRNAs play a crucial role in cancer development and progression. However, results on the impact of miRNAs on drug sensitivity and tumor biology vary, and most studies to date focussed on either increasing or decreasing miRNA expression levels. Therefore, the current study investigated the role of different expression levels of miR-130a-3p and miR-148a-3p on drug resistance and tumor biology in four esophageal squamous cell carcinoma cell lines. Interestingly, up- and downregulation of both miRNAs significantly increased sensitivity towards chemotherapy. MiRNA modulation also reduced adherence and migration potential, and increased apoptosis rates. Target analyses showed that up- and downregulation of both miRNAs activated the apoptotic p53-pathway via increased expression of either BAX (miR-148a-3p) or Caspase 9 (miR-130a-3p). miR-148a-3p downregulation seemed to mediate its effects primarily via regulation of Bim rather than Bcl-2 levels, whereas we found the opposite scenario following miR-148a-3p upregulation. A similar effect was observed for miR-130a-3p regulating Bcl-2 and XIAP. Our data provide the first evidence that miRNA modulation in both directions may lead to similar effects on chemotherapy response and tumor biology in esophageal squamous cell carcinoma. Most interestingly, up- and downregulation seem to mediate their effects via modulating the balance of several validated or predicted targets.

Original languageEnglish
Article number17553
JournalScientific Reports
Volume8
Issue number1
ISSN2045-2322
DOIs
Publication statusPublished - 01.12.2018

Research Areas and Centers

  • Research Area: Luebeck Integrated Oncology Network (LION)

Fingerprint

Dive into the research topics of 'Complex role of miR-130a-3p and miR-148a-3p balance on drug resistance and tumor biology in esophageal squamous cell carcinoma'. Together they form a unique fingerprint.

Cite this