STAT signalling in malignant mesothelioma: Is there a regulatory effect of microRNAs?

Abstract

PURPOSE: STAT1 and STAT3 are dysregulated in human malignant mesothelioma (MM), an aggressive cancer, with poor knowledge about predictive factors of outcome. Asbestos exposure is the main cause. Since microRNAs (miRNAs) are known to regulate the expression of target mRNAs, the aim of the study was to quantify selected miRNAs in MM which are thought to be involved in the STAT signalling pathway to gain more insight into a possible regulatory mechanism. PATIENTS: RNA was obtained from 35 formalin-fixed and paraffin-embedded tumour tissue samples. MATERIAL AND METHODS: MiRNAs were selected via in silico target prediction tools. Quantitative real-time PCR was used to assess the expression levels of the miRNAs. 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, and 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: An inverse correlation was found for pSTAT1 and miR-30d* (p = 0.014) 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.