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Arzt, L; Halbwedl, I; Gogg-Kamerer, M; Popper, HH.
Signal Transducer and Activator of Transcription 1 (STAT1) Knock-down Induces Apoptosis in Malignant Pleural Mesothelioma.
Pathol Oncol Res. 2017; 23(3):595-605 [OPEN ACCESS]
Web of Science PubMed FullText FullText_MUG

 

Autor/innen der Med Uni Graz:
Arzt-Gradwohl Lisa
Gogg-Kamerer Margit
Halbwedl Iris
Popper Helmuth
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Abstract:
Malignant pleural mesothelioma (MPM) is the most common primary tumor of the pleura. Its incidence is still increasing in Europe and the prognosis remains poor. We investigated the oncogenic function of signal transducer and activator of transcription 1 (STAT1) in MPM in more detail. A miRNA profiling was performed on 52 MPM tissue samples. Upregulated miRNAs (targeting SOCS1/3) were knocked-down using miRNA inhibitors. mRNA expression levels of STAT1/3, SOCS1/3 were detected in MPM cell lines. STAT1 has been knocked-down using siRNA and qPCR was used to detect mRNA expression levels of all JAK/STAT family members and genes that regulate them. An immunohistochemical staining was performed to detect the expression of caspases. STAT1 was upregulated and STAT3 was downregulated, SOCS1/3 protein was not detected but it was possible to detect SOCS1/3 mRNA in MPM cell lines. The upregulated miRNAs were successfully knocked-down, however the expected effect on SOCS1 expression was not detected. STAT1 knock-down had different effects on STAT3/5 expression. Caspase 3a and 8 expression was found to be increased after STAT1 knock-down. The physiologic regulation of STAT1 via SOCS1 is completely lost in MPM and it does not seem that the miRNAs identified by now, do inhibit the expression of SOCS1. MPM cell lines compensate STAT1 knock-down by increasing the expression of STAT3 or STAT5a, two genes which are generally considered to be oncogenes. And much more important, STAT1 knock-down induces apoptosis in MPM cell lines and STAT1 might therefore be a target for therapeutic intervention.
Find related publications in this database (using NLM MeSH Indexing)
Apoptosis - genetics
Carcinogenesis - genetics
Cell Line, Tumor -
Cell Proliferation - genetics
Down-Regulation - genetics
Gene Expression Regulation, Neoplastic - genetics
Humans -
Lung Neoplasms - genetics
Mesothelioma - genetics
MicroRNAs - genetics
Pleural Neoplasms - genetics
Prognosis -
RNA, Messenger - genetics
STAT1 Transcription Factor - genetics
STAT3 Transcription Factor - genetics
STAT5 Transcription Factor - genetics
Signal Transduction - genetics
Up-Regulation - genetics

Find related publications in this database (Keywords)
Malignant pleural mesothelioma
STAT signaling
miRNA
Apoptosis
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