Abstract
Background/Aims: STAT1 is up- and STAT3 is downregulated in human malignant mesothelioma (MM), a cancer with little knowledge about predictive factors of outcome. The negative feedback loop of STAT1 is not functioning: SOCS1 and PIAS1 are downregulated in MM. MicroRNAs (miRNAs) regulate the expression of target mRNA. Therefore we aimed to quantify selected miRNAs in MM which are thought to be involved in the regulation of the STAT signaling pathway.
Material/Methods: RNA was obtained from 35 formalin-fixed and paraffin-embedded tumor tissue samples. MiRNAs were selected via in silico target prediction tools. Quantitative real-time PCR was used to assess miRNA expression levels. The reference gene RNU6B was used for normalization. An immunohistochemical (IHC) staining with 5 antibodies was performed on tissue microarray sections to correlate it with the results of the miRNA detection.
Results: MiR-106a (targeting STAT3) expression was increased in 63% of cases. MiR-155, miR-19a and miR-30d* (targeting SOCS1, SOCS1 and STAT1, respectively) were downregulated in all cases. Due to very low expression levels, miR-196a*, miR-608 and miR-765 (targeting SOCS6, PIAS1, SOCS3 respectively) were not detected. Positive IHC staining was achieved for STAT1, pSTAT1(Ser727), STAT3 and PIAS1. STAT1 was higher expressed than STAT3; SOCS1 was not detected by IHC.
Conclusion: The inverse correlation between pSTAT1 and miR-30d* (p=0.014) indicates a regulatory effect and this miRNA may interact with STAT1 (p=0.062). STAT3 is not affected by miR-106a (p=0.53) although this miRNA is expected to play an important role in MM. Therefore additional targets have been selected which are currently investigated.
- © 2011 ERS