PSMB5 plays a dual role in cancer development and immunosuppression

Chih Yang Wang, Chung Yen Li, Hui Ping Hsu, Chien Yu Cho, Meng Chi Yen, Tzu Yang Weng, Wei Ching Chen, Yu Hsuan Hung, Kuo Ting Lee, Jui Hsiang Hung, Yi Ling Chen, Ming Derg Lai

研究成果: 雜誌貢獻文章

1 引文 (Scopus)

摘要

Tumor progression and metastasis are dependent on the intrinsic properties of tumor cells and the influence of microenvironment including the immune system. It would be important to identify target drug that can inhibit cancer cell and activate immune cells. Proteasome ß subunits (PSMB) family, one component of the ubiquitin-proteasome system, has been demonstrated to play an important role in tumor cells and immune cells. Therefore, we used a bioinformatics approach to examine the potential role of PSMB family. Analysis of breast TCGA and METABRIC database revealed that high expression of PSMB5 was observed in breast cancer tissue and that high expression of PSMB5 predicted worse survival. In addition, high expression of PSMB5 was observed in M2 macrophages. Based on our bioinformatics analysis, we hypothesized that PSMB5 contained immunosuppressive and oncogenic characteristics. To study the effects of PSMB5 on the cancer cell and macrophage in vitro, we silenced PSMB5 expression with shRNA in THP-1 monocytes and MDA-MB-231 cells respectively. Knockdown of PSMB5 promoted human THP-1 monocyte differentiation into M1 macrophage. On the other hand, knockdown PSMB5 gene expression inhibited MDA-MB-231 cell growth and migration by colony formation assay and boyden chamber. Collectively, our data demonstrated that delivery of PSMB5 shRNA suppressed cell growth and activated defensive M1 macrophages in vitro. Furthermore, lentiviral delivery of PSMB5 shRNA significantly decreased tumor growth in a subcutaneous mouse model. In conclusion, our bioinformatics study and functional experiments revealed that PSMB5 served as novel cancer therapeutic targets. These results also demonstrated a novel translational approach to improve cancer immunotherapy.
原文英語
頁(從 - 到)2103-2120
頁數18
期刊American Journal of Cancer Research
7
發行號11
出版狀態已發佈 - 一月 1 2017
對外發佈Yes

指紋

Immunosuppression
Neoplasms
Proteasome Endopeptidase Complex
Computational Biology
Macrophages
Small Interfering RNA
Monocytes
Growth
Cellular Microenvironment
Immunosuppressive Agents
Ubiquitin
Immunotherapy
Cell Movement
Immune System
Breast
Databases
Breast Neoplasms
Neoplasm Metastasis
Gene Expression
Survival

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

引用此文

Wang, C. Y., Li, C. Y., Hsu, H. P., Cho, C. Y., Yen, M. C., Weng, T. Y., ... Lai, M. D. (2017). PSMB5 plays a dual role in cancer development and immunosuppression. American Journal of Cancer Research, 7(11), 2103-2120.

PSMB5 plays a dual role in cancer development and immunosuppression. / Wang, Chih Yang; Li, Chung Yen; Hsu, Hui Ping; Cho, Chien Yu; Yen, Meng Chi; Weng, Tzu Yang; Chen, Wei Ching; Hung, Yu Hsuan; Lee, Kuo Ting; Hung, Jui Hsiang; Chen, Yi Ling; Lai, Ming Derg.

於: American Journal of Cancer Research, 卷 7, 編號 11, 01.01.2017, p. 2103-2120.

研究成果: 雜誌貢獻文章

Wang, CY, Li, CY, Hsu, HP, Cho, CY, Yen, MC, Weng, TY, Chen, WC, Hung, YH, Lee, KT, Hung, JH, Chen, YL & Lai, MD 2017, 'PSMB5 plays a dual role in cancer development and immunosuppression', American Journal of Cancer Research, 卷 7, 編號 11, 頁 2103-2120.
Wang CY, Li CY, Hsu HP, Cho CY, Yen MC, Weng TY 等. PSMB5 plays a dual role in cancer development and immunosuppression. American Journal of Cancer Research. 2017 1月 1;7(11):2103-2120.
Wang, Chih Yang ; Li, Chung Yen ; Hsu, Hui Ping ; Cho, Chien Yu ; Yen, Meng Chi ; Weng, Tzu Yang ; Chen, Wei Ching ; Hung, Yu Hsuan ; Lee, Kuo Ting ; Hung, Jui Hsiang ; Chen, Yi Ling ; Lai, Ming Derg. / PSMB5 plays a dual role in cancer development and immunosuppression. 於: American Journal of Cancer Research. 2017 ; 卷 7, 編號 11. 頁 2103-2120.
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title = "PSMB5 plays a dual role in cancer development and immunosuppression",
abstract = "Tumor progression and metastasis are dependent on the intrinsic properties of tumor cells and the influence of microenvironment including the immune system. It would be important to identify target drug that can inhibit cancer cell and activate immune cells. Proteasome {\ss} subunits (PSMB) family, one component of the ubiquitin-proteasome system, has been demonstrated to play an important role in tumor cells and immune cells. Therefore, we used a bioinformatics approach to examine the potential role of PSMB family. Analysis of breast TCGA and METABRIC database revealed that high expression of PSMB5 was observed in breast cancer tissue and that high expression of PSMB5 predicted worse survival. In addition, high expression of PSMB5 was observed in M2 macrophages. Based on our bioinformatics analysis, we hypothesized that PSMB5 contained immunosuppressive and oncogenic characteristics. To study the effects of PSMB5 on the cancer cell and macrophage in vitro, we silenced PSMB5 expression with shRNA in THP-1 monocytes and MDA-MB-231 cells respectively. Knockdown of PSMB5 promoted human THP-1 monocyte differentiation into M1 macrophage. On the other hand, knockdown PSMB5 gene expression inhibited MDA-MB-231 cell growth and migration by colony formation assay and boyden chamber. Collectively, our data demonstrated that delivery of PSMB5 shRNA suppressed cell growth and activated defensive M1 macrophages in vitro. Furthermore, lentiviral delivery of PSMB5 shRNA significantly decreased tumor growth in a subcutaneous mouse model. In conclusion, our bioinformatics study and functional experiments revealed that PSMB5 served as novel cancer therapeutic targets. These results also demonstrated a novel translational approach to improve cancer immunotherapy.",
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AU - Wang, Chih Yang

AU - Li, Chung Yen

AU - Hsu, Hui Ping

AU - Cho, Chien Yu

AU - Yen, Meng Chi

AU - Weng, Tzu Yang

AU - Chen, Wei Ching

AU - Hung, Yu Hsuan

AU - Lee, Kuo Ting

AU - Hung, Jui Hsiang

AU - Chen, Yi Ling

AU - Lai, Ming Derg

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AB - Tumor progression and metastasis are dependent on the intrinsic properties of tumor cells and the influence of microenvironment including the immune system. It would be important to identify target drug that can inhibit cancer cell and activate immune cells. Proteasome ß subunits (PSMB) family, one component of the ubiquitin-proteasome system, has been demonstrated to play an important role in tumor cells and immune cells. Therefore, we used a bioinformatics approach to examine the potential role of PSMB family. Analysis of breast TCGA and METABRIC database revealed that high expression of PSMB5 was observed in breast cancer tissue and that high expression of PSMB5 predicted worse survival. In addition, high expression of PSMB5 was observed in M2 macrophages. Based on our bioinformatics analysis, we hypothesized that PSMB5 contained immunosuppressive and oncogenic characteristics. To study the effects of PSMB5 on the cancer cell and macrophage in vitro, we silenced PSMB5 expression with shRNA in THP-1 monocytes and MDA-MB-231 cells respectively. Knockdown of PSMB5 promoted human THP-1 monocyte differentiation into M1 macrophage. On the other hand, knockdown PSMB5 gene expression inhibited MDA-MB-231 cell growth and migration by colony formation assay and boyden chamber. Collectively, our data demonstrated that delivery of PSMB5 shRNA suppressed cell growth and activated defensive M1 macrophages in vitro. Furthermore, lentiviral delivery of PSMB5 shRNA significantly decreased tumor growth in a subcutaneous mouse model. In conclusion, our bioinformatics study and functional experiments revealed that PSMB5 served as novel cancer therapeutic targets. These results also demonstrated a novel translational approach to improve cancer immunotherapy.

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KW - Macrophage

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