NDLI: Signal Transducer and Activator of Transcription 1 (STAT1) Knock-down Induces Apoptosis in Malignant Pleural Mesothelioma

Content Provider	Springer Nature Link
Author	Arzt, Lisa Halbwedl, Iris Gogg Kamerer, Margit Popper, Helmut H.
Copyright Year	2016
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.
Starting Page	595
Ending Page	605
Page Count	11
File Format	PDF
ISSN	12194956
Journal	Pathology & Oncology Research
Volume Number	23
Issue Number	3
e-ISSN	15322807
Language	English
Publisher	Springer Netherlands
Publisher Date	2016-12-16
Publisher Place	Dordrecht
Access Restriction	Subscribed
Subject Keyword	Malignant pleural mesothelioma STAT signaling miRNA Apoptosis Cancer Research Oncology Pathology Immunology Biomedicine
Content Type	Text
Resource Type	Article
Subject	Cancer Research Pathology and Forensic Medicine Oncology

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