SHP2, SOCS3 and PIAS3 Expression Patterns in Medulloblastomas: Relevance to STAT3 Activation and Resveratrol-Suppressed STAT3 Signaling
Background: Activated STAT3 signaling is critical for human medulloblastoma cells. SHP2, SOCS3 and PIAS3 are known as the negative regulators of STAT3 signaling, while their relevance to frequent STAT3 activation in medulloblastomas remains unknown. Methods: Tissue microarrays were constructed with...
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doaj-84c144cc90a348d589e82d78c1336b932020-11-25T00:49:12ZengMDPI AGNutrients2072-66432016-12-0191310.3390/nu9010003nu9010003SHP2, SOCS3 and PIAS3 Expression Patterns in Medulloblastomas: Relevance to STAT3 Activation and Resveratrol-Suppressed STAT3 SignalingCong Li0Hong Li1Peng Zhang2Li-Jun Yu3Tian-Miao Huang4Xue Song5Qing-You Kong6Jian-Li Dong7Pei-Nan Li8Jia Liu9Liaoning Laboratory of Cancer Genetics and Epigenetics and Department of Cell Biology, Dalian Medical University, Dalian 116044, ChinaLiaoning Laboratory of Cancer Genetics and Epigenetics and Department of Cell Biology, Dalian Medical University, Dalian 116044, ChinaLiaoning Laboratory of Cancer Genetics and Epigenetics and Department of Cell Biology, Dalian Medical University, Dalian 116044, ChinaLiaoning Laboratory of Cancer Genetics and Epigenetics and Department of Cell Biology, Dalian Medical University, Dalian 116044, ChinaLiaoning Laboratory of Cancer Genetics and Epigenetics and Department of Cell Biology, Dalian Medical University, Dalian 116044, ChinaLiaoning Laboratory of Cancer Genetics and Epigenetics and Department of Cell Biology, Dalian Medical University, Dalian 116044, ChinaLiaoning Laboratory of Cancer Genetics and Epigenetics and Department of Cell Biology, Dalian Medical University, Dalian 116044, ChinaDepartment of Orthopedic Surgery, Second Hospital of Dalian Medical University, Dalian 116011, ChinaDepartment of Orthopedic Surgery, Second Hospital of Dalian Medical University, Dalian 116011, ChinaLiaoning Laboratory of Cancer Genetics and Epigenetics and Department of Cell Biology, Dalian Medical University, Dalian 116044, ChinaBackground: Activated STAT3 signaling is critical for human medulloblastoma cells. SHP2, SOCS3 and PIAS3 are known as the negative regulators of STAT3 signaling, while their relevance to frequent STAT3 activation in medulloblastomas remains unknown. Methods: Tissue microarrays were constructed with 17 tumor-surrounding noncancerous brain tissues and 61 cases of the classic medulloblastomas, 44 the large-cell medulloblastomas, and 15 nodular medulloblastomas, which were used for immunohistochemical profiling of STAT3, SHP2, SOCS3 and PIAS3 expression patterns and the frequencies of STAT3 nuclear translocation. Three human medulloblastoma cell lines (Daoy, UW228-2 and UW228-3) were cultured with and without 100 μM resveratrol supplementation. The influences of resveratrol in SHP2, SOCS3 and PIAS3 expression and SOCS3 knockdown in STAT3 activation were analyzed using multiple experimental approaches. Results: SHP2, SOCS3 and PIAS3 levels are reduced in medulloblastomas in vivo and in vitro, of which PIAS3 downregulation is more reversely correlated with STAT3 activation. In resveratrol-suppressed medulloblastoma cells with STAT3 downregulation and decreased incidence of STAT3 nuclear translocation, PIAS3 is upregulated, the SHP2 level remains unchanged and SOCS3 is downregulated. SOCS3 proteins are accumulated in the distal ends of axon-like processes of resveratrol-differentiated medulloblastoma cells. Knockdown of SOCS3 expression by siRNA neither influences cell proliferation nor STAT3 activation or resveratrol sensitivity but inhibits resveratrol-induced axon-like process formation. Conclusion: Our results suggest that (1) the overall reduction of SHP2, SOCS3 and PIAS3 in medulloblastoma tissues and cell lines; (2) the more inverse relevance of PIAS3 expression with STAT3 activation; (3) the favorable prognostic values of PIAS3 for medulloblastomas and (4) the involvement of SOCS3 in resveratrol-promoted axon regeneration of medulloblastoma cells.http://www.mdpi.com/2072-6643/9/1/3medulloblastomaSTAT3 signalingSTAT3 negative regulatorsPIAS3resveratrol |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Cong Li Hong Li Peng Zhang Li-Jun Yu Tian-Miao Huang Xue Song Qing-You Kong Jian-Li Dong Pei-Nan Li Jia Liu |
spellingShingle |
Cong Li Hong Li Peng Zhang Li-Jun Yu Tian-Miao Huang Xue Song Qing-You Kong Jian-Li Dong Pei-Nan Li Jia Liu SHP2, SOCS3 and PIAS3 Expression Patterns in Medulloblastomas: Relevance to STAT3 Activation and Resveratrol-Suppressed STAT3 Signaling Nutrients medulloblastoma STAT3 signaling STAT3 negative regulators PIAS3 resveratrol |
author_facet |
Cong Li Hong Li Peng Zhang Li-Jun Yu Tian-Miao Huang Xue Song Qing-You Kong Jian-Li Dong Pei-Nan Li Jia Liu |
author_sort |
Cong Li |
title |
SHP2, SOCS3 and PIAS3 Expression Patterns in Medulloblastomas: Relevance to STAT3 Activation and Resveratrol-Suppressed STAT3 Signaling |
title_short |
SHP2, SOCS3 and PIAS3 Expression Patterns in Medulloblastomas: Relevance to STAT3 Activation and Resveratrol-Suppressed STAT3 Signaling |
title_full |
SHP2, SOCS3 and PIAS3 Expression Patterns in Medulloblastomas: Relevance to STAT3 Activation and Resveratrol-Suppressed STAT3 Signaling |
title_fullStr |
SHP2, SOCS3 and PIAS3 Expression Patterns in Medulloblastomas: Relevance to STAT3 Activation and Resveratrol-Suppressed STAT3 Signaling |
title_full_unstemmed |
SHP2, SOCS3 and PIAS3 Expression Patterns in Medulloblastomas: Relevance to STAT3 Activation and Resveratrol-Suppressed STAT3 Signaling |
title_sort |
shp2, socs3 and pias3 expression patterns in medulloblastomas: relevance to stat3 activation and resveratrol-suppressed stat3 signaling |
publisher |
MDPI AG |
series |
Nutrients |
issn |
2072-6643 |
publishDate |
2016-12-01 |
description |
Background: Activated STAT3 signaling is critical for human medulloblastoma cells. SHP2, SOCS3 and PIAS3 are known as the negative regulators of STAT3 signaling, while their relevance to frequent STAT3 activation in medulloblastomas remains unknown. Methods: Tissue microarrays were constructed with 17 tumor-surrounding noncancerous brain tissues and 61 cases of the classic medulloblastomas, 44 the large-cell medulloblastomas, and 15 nodular medulloblastomas, which were used for immunohistochemical profiling of STAT3, SHP2, SOCS3 and PIAS3 expression patterns and the frequencies of STAT3 nuclear translocation. Three human medulloblastoma cell lines (Daoy, UW228-2 and UW228-3) were cultured with and without 100 μM resveratrol supplementation. The influences of resveratrol in SHP2, SOCS3 and PIAS3 expression and SOCS3 knockdown in STAT3 activation were analyzed using multiple experimental approaches. Results: SHP2, SOCS3 and PIAS3 levels are reduced in medulloblastomas in vivo and in vitro, of which PIAS3 downregulation is more reversely correlated with STAT3 activation. In resveratrol-suppressed medulloblastoma cells with STAT3 downregulation and decreased incidence of STAT3 nuclear translocation, PIAS3 is upregulated, the SHP2 level remains unchanged and SOCS3 is downregulated. SOCS3 proteins are accumulated in the distal ends of axon-like processes of resveratrol-differentiated medulloblastoma cells. Knockdown of SOCS3 expression by siRNA neither influences cell proliferation nor STAT3 activation or resveratrol sensitivity but inhibits resveratrol-induced axon-like process formation. Conclusion: Our results suggest that (1) the overall reduction of SHP2, SOCS3 and PIAS3 in medulloblastoma tissues and cell lines; (2) the more inverse relevance of PIAS3 expression with STAT3 activation; (3) the favorable prognostic values of PIAS3 for medulloblastomas and (4) the involvement of SOCS3 in resveratrol-promoted axon regeneration of medulloblastoma cells. |
topic |
medulloblastoma STAT3 signaling STAT3 negative regulators PIAS3 resveratrol |
url |
http://www.mdpi.com/2072-6643/9/1/3 |
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