Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
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
Doi: 10.1007/s12253-016-0157-3
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- Führende Autor*innen der Med Uni Graz
- Arzt-Gradwohl Lisa
- Co-Autor*innen der Med Uni Graz
- 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