miR-199a-5p regulates and and its expression is correlated to soft-tissue sarcoma patients' outcome.

Soft tissue sarcomas are a heterogeneous group of malignant neoplasms of mesenchymal origin. Partly due to hypoxia, an aggressive and radioresistant phenotype frequently develops, resulting in poorer patient outcome. microRNAs (miRNAs) are tiny, non-coding regulators of gene expression and in situations of cellular stress situations may predict clinical progression and patient outcome. In the present study, hypoxia-associated miR-199a-5p expression in 96 soft tissue sarcoma samples was analysed by reverse transcription-quantitative polymerase chain reaction and associations between miR-199a-5p expression and patient clinicopathological characteristics and survival were measured. Additionally, luciferase reporter assays analyzed the post-transcriptional regulation of hypoxia-associated genes hypoxia-inducible factor 1α (α), oxidative stress induced growth inhibitor 2 () and vascular endothelial growth factor () by miR-199a-5p. Survival analyses indicated that low expression of miR-199a-5p was significantly correlated with poorer tumor-specific survival (univariate Cox's-Regression analyses; relative risk=1.92, P=0.029). Furthermore, it was demonstrated that the 3'UTR of α and genes were regulated by miR-199a-5p , although the 3'UTR of was not. To the best of our knowledge, this is the first report demonstrating the regulation of the 3'untranslated region of the gene by miR-199a-5p and a significant correlation between low miR-199a-5p expression and a poor outcome of patients with soft tissue sarcoma.