MicroRNA response to hypoxic stress in soft tissue sarcoma cells: microRNA mediated regulation of HIF3α

• Published in: BMC cancer 2014-06, Vol.14 (1), p.429-429, Article 429
• Main Authors: Gits, Caroline M M, van Kuijk, Patricia F, de Rijck, Jonneke C W M, Muskens, Nikky, Jonkers, Moniek B E, van IJcken, Wilfred F, Mathijssen, Ron H J, Verweij, Jaap, Sleijfer, Stefan, Wiemer, Erik A C
• Format: Article
• Language: English
• Subjects: Basic Helix-Loop-Helix Transcription Factors - biosynthesis; Basic Helix-Loop-Helix Transcription Factors - genetics; Cell Hypoxia - genetics; Cell Line, Tumor; Gene Expression Regulation, Neoplastic; Humans; MicroRNAs - genetics; Prognosis; Sarcoma - genetics; Sarcoma - pathology; Signal Transduction
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/1471-2407-14-429

Hypoxia is often encountered in solid tumors and known to contribute to aggressive tumor behavior, radiation- and chemotherapy resistance resulting in a poor prognosis for the cancer patient. MicroRNAs (miRNAs) play a role in the regulation of the tumor cell response to hypoxia, however, not much is known about the involvement of miRNAs in hypoxic signalling pathways in soft tissue sarcomas (STS). A panel of twelve STS cell lines was exposed to atmospheric oxygen concentrations (normoxia) or 1% oxygen (hypoxia) for up to 48 h. Hypoxic conditions were verified and miRNA expression profiles were assessed by LNA™ oligonucleotide microarrays and RT-PCR after 24 h. The expression of target genes regulated by hypoxia responsive miRNAs is examined by end-point PCR and validated by luciferase reporter constructs. Exposure of STS cell lines to hypoxic conditions gave rise to upregulation of Hypoxia Inducible Factor (HIF) 1α protein levels and increased mRNA expression of HIF1 target genes CA9 and VEGFA. Deregulation of miRNA expression after 24 h of hypoxia was observed. The most differentially expressed miRNAs (p