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

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)2103-2120
Number of pages18
JournalAmerican Journal of Cancer Research
Volume7
Issue number11
Publication statusPublished - 2017 Jan 1

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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

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

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.
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. In: American Journal of Cancer Research. 2017 ; Vol. 7, No. 11. pp. 2103-2120.
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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.",
author = "Wang, {Chih Yang} and Li, {Chung Yen} and Hui-Ping Hsu and Cho, {Chien Yu} and Yen, {Meng Chi} and Weng, {Tzu Yang} and Chen, {Wei Ching} and Hung, {Yu Hsuan} and Kuo-Ting Lee and Hung, {Jui Hsiang} and Chen, {Yi Ling} and Ming-Derg Lai",
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Wang, CY, Li, CY, Hsu, H-P, Cho, CY, Yen, MC, Weng, TY, Chen, WC, Hung, YH, Lee, K-T, Hung, JH, Chen, YL & Lai, M-D 2017, 'PSMB5 plays a dual role in cancer development and immunosuppression', American Journal of Cancer Research, vol. 7, no. 11, pp. 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.

In: American Journal of Cancer Research, Vol. 7, No. 11, 01.01.2017, p. 2103-2120.

Research output: Contribution to journalArticle

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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

PY - 2017/1/1

Y1 - 2017/1/1

N2 - 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.

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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Wang CY, Li CY, Hsu H-P, Cho CY, Yen MC, Weng TY et al. PSMB5 plays a dual role in cancer development and immunosuppression. American Journal of Cancer Research. 2017 Jan 1;7(11):2103-2120.