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Shine Gwo Shiah - One of the best experts on this subject based on the ideXlab platform.
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mir 944 CISH mediated inflammation via stat3 is involved in oral cancer malignance by cigarette smoking
Neoplasia, 2020Co-Authors: Hsuan Yu Peng, Jenn Ren Hsiao, Sung Tau Chou, Yuan Ming Hsu, Yi Shing Shieh, Shine Gwo ShiahAbstract:The cytokine-inducible Src homology 2-containing protein (CISH) is an endogenous suppressors of signal transduction and activator of transcription (STAT) and acts as a key negative regulator of inflammatory cytokine responses. Downregulation of CISH has been reported to associate with increased activation of STAT and enhanced inflammatory pathways. However, whether microRNAs (miRNAs) play a crucial role in CISH/STAT regulation in oral squamous cell carcinoma (OSCC) remains unknown. The expression of CISH on OSCC patients was determine by quantitative real-time PCR (qRT-PCR) and immunohistochemistry. Specific targeting by miRNAs was determined by software prediction, luciferase reporter assay, and correlation with target protein expression. The functions of miR-944 and CISH were accessed by transwell migration and invasion analyses using gain- and loss-of-function approaches. Enzyme-linked immunosorbent assay (ELISA) and qRT-PCR were used to evaluate the pro-inflammation cytokines expression under the miR-944, CISH, NNK or combinations treatment. We found that the CISH protein, which modulates STAT3 activity, as a direct target of miR-944. CISH protein was significantly down-regulated in OSCC patients and cell lines and its level was inversely correlated with miR-944 expression. The miR-944-induced STAT3 phosphorylation, pro-inflammation cytokines secretion, migration and invasion were abolished by CISH restoration, suggesting that the oncogenic activity of miR-944 is CISH dependent. Furthermore, tobacco extract (NNK) may contribute to miR-944 induction and STAT3 activation. Antagomir-mediated inactivation of miR-944 prevented the NNK-induced STAT3 phosphorylation and pro-inflammation cytokines secretion. Altogether, these data demonstrate that NNK-induced miR944 expression plays an important role in CISH/STAT3-mediated inflammatory response and activation of tumor malignancy.
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mir 944 CISH mediated inflammation via stat3 is involved in oral cancer malignance by cigarette smoking
Social Science Research Network, 2020Co-Authors: Hsuan Yu Peng, Jenn Ren Hsiao, Sung Tau Chou, Yuan Ming Hsu, Yi Shing Shieh, Shine Gwo ShiahAbstract:Background: The cytokine-inducible Src homology 2-containing protein (CISH) is an endogenous suppressors of signal transduction and activator of transcription (STAT) and acts as a key negative regulator of inflammatory cytokine responses. Downregulation of CISH has been reported to associate with increased activation of STAT and enhanced inflammatory pathways. However, whether microRNAs (miRNAs) play a crucial role in CISH/STAT regulation and its underlying mechanism in oral squamous cell carcinoma (OSCC) remains unknown. Methods: The expression of CISH on OSCC patients was determine by quantitative real-time PCR (qRT-PCR) and immunohistochemistry. Specific targeting by miRNAs was determined by software prediction and luciferase reporter assay. The functions of miR-944 and CISH were accessed by transwell migration and invasion analyses using gain- and loss-of-function approaches. Enzyme-linked immunosorbent assay and qRT-PCR were used to evaluate the pro-inflammation cytokines expression under the miR-944, CISH, NNK or combinations treatment. Findings: CISH protein was significantly down-regulated in OSCC patients and cell lines and its level was inversely correlated with miR-944 expression. MiR-944-induced STAT3 phosphorylation, pro-inflammation cytokines secretion, migration and invasion were abolished by CISH restoration. Furthermore, tobacco extract (NNK) may contribute to the miR-944 induction and the activation of STAT3 in OSCC. MiR-944 inhibitor prevented the NNK-induced STAT3 phosphorylation and pro-inflammation cytokines secretion, indicating that miR-944 is required for NNK-induced cellular inflammatory pathways. Interpretation: Altogether, these data demonstrate that NNK-induced miR-944 expression plays an important role in CISH/STAT3-mediated inflammatory response and activation of tumor malignancy. Funding: This work was supported by National Health Research Institutes (NHRI) grants from Taiwan (NHRI-CA107-PP03, NHRI-CA108-PP03), and the Ministry of Health and Welfare (MOHW) grants from Taiwan (MOHW 108-TDU-B-212-124026, MOHW 109-TDU-B-212-134013). Declaration of Interests: The authors declare that they have no competing interests. Ethics Approval Statement: The study protocol was approved by the Research Ethics Committee of National Health Research Institutes (EC1040409-E) and Institutional Human Experiment and Ethic Committee of National Cheng Kung University Hospital (HR-97-100) for the use of clinical materials for research purpose. Informed consent was obtained from each patient.
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NNK induces miR-944 expression and modulates CISH/STAT3 signaling pathway in oral squamous cell carcinoma
'Wiley', 2019Co-Authors: Shine Gwo ShiahAbstract:[[abstract]]The cytokine-inducible Src homology 2-containing protein (CISH) is an endogenous suppressors of signal transduction and activator of transcription (STAT) and acts as a key negative regulator of inflammatory cytokine responses. Downregulation of CISH has been reported to associate with increased activation of STAT and enhanced inflammatory pathways. However, the underlying mechanisms of dysregulation of CISH/STAT pathway in oral squamous cell carcinoma (OSCC) remains unknown. Here, we report that CISH protein is significantly downregulated in OSCC patients and its levels are inversely correlated with miR-944 expression. We identified the CISH protein, which modulates STAT3 activity, as a direct target of miR-944. The miR-944-mediated CISH functions are crucial in regulating STAT3 activity, pro-inflammation molecules secretion (such as CCL3, CCL5, IL-1Ra and IL-1β), migration and invasive potential in OSCC cells. Furthermore, the expression of miR-944 was significantly induced by the 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and co-expressed with its host gene TP63. Taken together, miR-944/CISH/STAT3 may have therapeutic potential for the treatment of OSCC
Christopher J. Secombes - One of the best experts on this subject based on the ideXlab platform.
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Four CISH paralogues are present in rainbow trout Oncorhynchus mykiss: Differential expression and modulation during immune responses and development
Molecular immunology, 2014Co-Authors: Tanja Maehr, Tiehui Wang, Jose L. González Vecino, Simon Wadsworth, Christopher J. SecombesAbstract:Suppressor of cytokine signalling (SOCS) family members are crucial in the control and attenuation of cytokine induced responses via activation of the JAK/STAT, TLR and NF-kB signalling pathways. SOCS proteins orchestrate the termination of many types of immune responses and are often the targets of microbial pathogens exploiting SOCS mechanisms to evade the host's immune response. Through whole and lineage specific genome duplication events, the teleost cytokine/SOCS network is complex. Not only are the orthologues of all mammalian SOCS members present, namely cytokine inducible Src homology 2 (SH2)-containing protein (CISH) and SOCS-1 to -7, but multiple gene copies exist that may potentially become functionally divergent. In this paper we focus on the CISH genes in rainbow trout (Oncorhynchus mykiss), and have cloned two further paralogues, CISHa2 and CISHb2, additional to the known CISHa1 and CISHb1 genes. We present for the first time a comparative expression analysis of these four paralogues, to establish whether subfunctionalisation is apparent. In vivo examination of gene expression revealed a higher constitutive expression level of CISHa paralogues compared to CISHb expression in adult trout tissues. All CISHs were relatively highly abundant in immune tissues but CISHa2 and CISHb2 had highest expression in the heart and muscle. An inverse picture of CISH abundance during trout ontogeny was seen, and further hints at differential roles of the four genes in immune regulation and development. Stimulation of head kidney (HK) leukocytes with trout recombinant interleukin (rIL)-15 and rIL-21 had a major effect on CISHa2 and to a lesser extent CISHa1 expression. In HK macrophages rIL-1β, phytohemagglutinin, and phorbol 12-myristate 13-acetate also had a strong impact on CISHa2 expression. Yersinia ruckeri infection caused a temporally and spatially differential onset of CISH expression that may be viewed in the context of pathogen evasion strategies. These data, against the backdrop of fish specific whole genome duplication events and functional divergence, provide the first evidence for differential roles of the four trout CISH genes in immune control and development.
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Identification of suppressor of cytokine signalling (SOCS) 6, 7, 9 and CISH in rainbow trout Oncorhynchus mykiss and analysis of their expression in relation to other known trout SOCS
Fish & shellfish immunology, 2010Co-Authors: Tiehui Wang, Qian Gao, Pin Nie, Christopher J. SecombesAbstract:Four new members of the SOCS family of molecules in rainbow trout (Oncorhynchus mykiss), CISH and SOCS6, 7 and 9, are described for the first time in this species. The genes had a wide tissue distribution in trout, and were detected in gills, skin, muscle, liver, spleen, head kidney, intestine and brain, with brain having the highest expression levels. Stimulation of a rainbow trout leucocyte cell line, RTS-11, (mononuclear/macrophage-like cells) with LPS or Poly 1:C had no effect on the expression of these genes, although in both cases the previously identified SOCS1-3 genes were up-regulated. Similarly, stimulation of RTS-11 or RTG-2 (fibroblasts) cells with the trout recombinant cytokines IFN-gamma or IL-1 beta had no effect on CISH or SOCS6, 7 and 9 expression. However, PMA stimulation did impact on SOCS6 and SOCS9 expression, and LPS stimulation of primary cultures or bacterial infection (Yersinia ruckeri) increased significantly CISH expression (as well as SOCS1 and SOCS2 or SOCS3 respectively). It is apparent that the type II SOCS genes (CISH, SOCS1-3) are particularly relevant to immune regulation in fish, although the intriguing expansion of the SOCS4/5 subgroup in fish requires further investigation as to their role and functional divergence. (C) 2010 Elsevier Ltd. All rights reserved.
Hsuan Yu Peng - One of the best experts on this subject based on the ideXlab platform.
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mir 944 CISH mediated inflammation via stat3 is involved in oral cancer malignance by cigarette smoking
Neoplasia, 2020Co-Authors: Hsuan Yu Peng, Jenn Ren Hsiao, Sung Tau Chou, Yuan Ming Hsu, Yi Shing Shieh, Shine Gwo ShiahAbstract:The cytokine-inducible Src homology 2-containing protein (CISH) is an endogenous suppressors of signal transduction and activator of transcription (STAT) and acts as a key negative regulator of inflammatory cytokine responses. Downregulation of CISH has been reported to associate with increased activation of STAT and enhanced inflammatory pathways. However, whether microRNAs (miRNAs) play a crucial role in CISH/STAT regulation in oral squamous cell carcinoma (OSCC) remains unknown. The expression of CISH on OSCC patients was determine by quantitative real-time PCR (qRT-PCR) and immunohistochemistry. Specific targeting by miRNAs was determined by software prediction, luciferase reporter assay, and correlation with target protein expression. The functions of miR-944 and CISH were accessed by transwell migration and invasion analyses using gain- and loss-of-function approaches. Enzyme-linked immunosorbent assay (ELISA) and qRT-PCR were used to evaluate the pro-inflammation cytokines expression under the miR-944, CISH, NNK or combinations treatment. We found that the CISH protein, which modulates STAT3 activity, as a direct target of miR-944. CISH protein was significantly down-regulated in OSCC patients and cell lines and its level was inversely correlated with miR-944 expression. The miR-944-induced STAT3 phosphorylation, pro-inflammation cytokines secretion, migration and invasion were abolished by CISH restoration, suggesting that the oncogenic activity of miR-944 is CISH dependent. Furthermore, tobacco extract (NNK) may contribute to miR-944 induction and STAT3 activation. Antagomir-mediated inactivation of miR-944 prevented the NNK-induced STAT3 phosphorylation and pro-inflammation cytokines secretion. Altogether, these data demonstrate that NNK-induced miR944 expression plays an important role in CISH/STAT3-mediated inflammatory response and activation of tumor malignancy.
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mir 944 CISH mediated inflammation via stat3 is involved in oral cancer malignance by cigarette smoking
Social Science Research Network, 2020Co-Authors: Hsuan Yu Peng, Jenn Ren Hsiao, Sung Tau Chou, Yuan Ming Hsu, Yi Shing Shieh, Shine Gwo ShiahAbstract:Background: The cytokine-inducible Src homology 2-containing protein (CISH) is an endogenous suppressors of signal transduction and activator of transcription (STAT) and acts as a key negative regulator of inflammatory cytokine responses. Downregulation of CISH has been reported to associate with increased activation of STAT and enhanced inflammatory pathways. However, whether microRNAs (miRNAs) play a crucial role in CISH/STAT regulation and its underlying mechanism in oral squamous cell carcinoma (OSCC) remains unknown. Methods: The expression of CISH on OSCC patients was determine by quantitative real-time PCR (qRT-PCR) and immunohistochemistry. Specific targeting by miRNAs was determined by software prediction and luciferase reporter assay. The functions of miR-944 and CISH were accessed by transwell migration and invasion analyses using gain- and loss-of-function approaches. Enzyme-linked immunosorbent assay and qRT-PCR were used to evaluate the pro-inflammation cytokines expression under the miR-944, CISH, NNK or combinations treatment. Findings: CISH protein was significantly down-regulated in OSCC patients and cell lines and its level was inversely correlated with miR-944 expression. MiR-944-induced STAT3 phosphorylation, pro-inflammation cytokines secretion, migration and invasion were abolished by CISH restoration. Furthermore, tobacco extract (NNK) may contribute to the miR-944 induction and the activation of STAT3 in OSCC. MiR-944 inhibitor prevented the NNK-induced STAT3 phosphorylation and pro-inflammation cytokines secretion, indicating that miR-944 is required for NNK-induced cellular inflammatory pathways. Interpretation: Altogether, these data demonstrate that NNK-induced miR-944 expression plays an important role in CISH/STAT3-mediated inflammatory response and activation of tumor malignancy. Funding: This work was supported by National Health Research Institutes (NHRI) grants from Taiwan (NHRI-CA107-PP03, NHRI-CA108-PP03), and the Ministry of Health and Welfare (MOHW) grants from Taiwan (MOHW 108-TDU-B-212-124026, MOHW 109-TDU-B-212-134013). Declaration of Interests: The authors declare that they have no competing interests. Ethics Approval Statement: The study protocol was approved by the Research Ethics Committee of National Health Research Institutes (EC1040409-E) and Institutional Human Experiment and Ethic Committee of National Cheng Kung University Hospital (HR-97-100) for the use of clinical materials for research purpose. Informed consent was obtained from each patient.
Jorma Isola - One of the best experts on this subject based on the ideXlab platform.
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performance of chromogenic in situ hybridization on testing her2 status in breast carcinomas with chromosome 17 polysomy and equivocal 2 herceptest results a study of two institutions using the conventional and new asco cap scoring criteria
American Journal of Clinical Pathology, 2009Co-Authors: Yun Gong, Jorma Isola, William Sweet, Yi Jing Duh, Larry Greenfield, Emily Tarco, Smita Trivedi, Fraser W Symmans, Nour SneigeAbstract:This study specifically addressed the performance of chromogenic in situ hybridization (CISH) on HER2 testing in 66 breast carcinomas with chromosome 17 polysomy and 49 carcinomas with an equivocal HercepTest (DakoCytomation, Carpinteria, CA) score by comparing CISH with corresponding FISH results at 2 test sites and evaluating intersite agreement of CISH results. For tumors with chromosome 17 polysomy, when using the manufacturers’ criteria, the concordance values between CISH and FISH at site A, site B, and intersite CISH agreement were 95.8%, 95.5%, and 93.5%, respectively; when using the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) criteria, the values were 100.0%, 100.0%, and 100.0%, respectively. For tumors with an equivocal HercepTest score, when using the manufacturers’ criteria, the concordance values between the 2 methods at site A, site B, and intersite CISH agreement were 88.2%, 95.1%, and 91.1%, respectively; when using the ASCO/CAP criteria, the values were 96.7%, 97.3%, and 97.4%, respectively. These results indicate that CISH is reliable for testing these 2 types of tumors, especially when the ASCO/CAP criteria are used.
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interlaboratory comparison of her 2 oncogene amplification as detected by chromogenic and fluorescence in situ hybridization
Clinical Cancer Research, 2004Co-Authors: Jorma Isola, Minna Tanner, Amanda Forsyth, T G Cooke, A D Watters, John M S BartlettAbstract:Purpose: Chromogenic in situ hybridization (CISH) is a new modification of the fluorescence in situ hybridization (FISH) technique for detection of oncogene amplification in archival tumor samples. In CISH, the oncogene probe is detected using a peroxidase reaction, allowing use of transmitted light microscopy. We compared detection of HER-2 / neu amplification by CISH with a Food and Drug Administration-approved two-color FISH test in an interlaboratory setting. Experimental Design: Formalin-fixed paraffin-embedded tumor samples from 197 breast cancers were analyzed for HER-2 amplification by CISH. Two-color FISH (PathVysion) CISH of 17 centromere was done if the observer considered it necessary to ascertain amplification status in tumors with borderline HER-2 CISH copy numbers. Results: Paired CISH/FISH results were available from 192 (97%) of 197 cases, no clear difference in success rates of either method was observed. Centromere 17 CISH was considered necessary in seven tumors. CISH and two-color FISH results were concordant in 180 cases (93.8%). There were 92 and 88 tumors found HER-2 amplified and nonamplified, respectively, by both methods. Eight tumors were amplified by CISH but not by FISH, and four tumors exhibited the opposite condition (kappa coefficient 0.875). In 7 of 12 cases differences between the two methods could have related to a lack of CISH chromosome 17 information. The remaining cases were explained by difficult histology (ductal carcinoma in situ , poor representativity, dense lymphocytic infiltration, or intratumoral heterogeneity). Conclusions: These results indicate that CISH could provide an accurate and practical alternative to FISH for clinical diagnosis of HER-2/neu oncogene amplification in archival formalin-fixed breast cancer samples.
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chromogenic in situ hybridization a practical alternative for fluorescence in situ hybridization to detect her 2 neu oncogene amplification in archival breast cancer samples
American Journal of Pathology, 2000Co-Authors: Minna Tanner, David Gancberg, Angelo Di Leo, Denis Larsimont, Ghizlane Rouas, Martine Piccart, Jorma IsolaAbstract:Determination of HER-2/neu oncogene amplification has become necessary for selection of breast cancer patients for trastuzumab (Herceptin) therapy. Fluorescence in situ hybridization (FISH) is currently regarded as a gold standard method for detecting HER-2/neu amplification, but it is not very practical for routine histopathological laboratories. We evaluated a new modification of in situ hybridization, the chromogenic in situ hybridization (CISH), which enables detection of HER-2/neu gene copies with conventional peroxidase reaction. Archival formalin-fixed paraffin-embedded tumor tissue sections were pretreated (by heating in a microwave oven and using enzyme digestion) and hybridized with a digoxigenin-labeled DNA probe. The probe was detected with anti-digoxigenin fluorescein, anti-fluorescein peroxidase, and diaminobenzidine. Gene copies visualized by CISH could be easily distinguished with a ×40 objective in hematoxylin-stained tissue sections. HER-2/neu amplification typically appeared as large peroxidase-positive intranuclear gene copy clusters. CISH and FISH (according to Vysis, made from frozen pulverized tumor samples) correlated well in a series of 157 breast cancers (kappa coefficient, 0.81). The few different classifications were mostly because of low-level amplifications by FISH that were negative by CISH and immunohistochemistry with monoclonal antibody CB-11. We conclude that CISH, using conventional bright-field microscopy in evaluation, is a useful alternative for determination of HER-2/neu amplification in paraffin-embedded tumor samples, especially for confirming the immunohistochemical staining results.
Jacki Abrams - One of the best experts on this subject based on the ideXlab platform.
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comparison of fluorescence and chromogenic in situ hybridization for detection of her 2 neu oncogene in breast cancer
American Journal of Clinical Pathology, 2003Co-Authors: Deepali Gupta, Lavinia P Middleton, Marion J Whitaker, Jacki AbramsAbstract:Determination of HER-2/neu oncogene amplification has become clinically important in the present management of breast cancer and may have important applications in other areas of clinical oncology and scientific research. In situ hybridization is an extremely accurate and sensitive technique for assessing amplification of HER-2/neu. A new method using a chromogen-labeled probe offers numerous advantages, including the ability to view the morphologic features of the cells of interest using a light microscope, which can be found in every laboratory. We used both techniques to assay 31 cases of infiltrating breast carcinoma; assays were performed in laboratories at 2 institutions. Identical results for both methods were found in 26 cases (10 amplified, 16 nonamplified). One case was misinterpreted as overexpressed by chromogenic in situ hybridization (CISH) because of background precipitate. In 4 cases, CISH suggested low-level amplification. Three of these cases subsequently were found to have chromosome 17 polysomy. In the remaining case, the initial section chosen was suboptimal, showing weak signals by both methods. If a probe for chromosome 17 (now available for CISH) is used in cases of questionable HER-2/neu amplification, CISH seems to be as accurate and more practical than FISH.