PSMB5 plays a dual role in cancer development and immunosuppression

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標題:	PSMB5 plays a dual role in cancer development and immunosuppression
作者:	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
貢獻者:	Natl Cheng Kung Univ, Dept Biochem & Mol Biol Natl Cheng Kung Univ, Inst Basic Med Sci Natl Cheng Kung Univ, Dept Surg, Coll Med Kaohsiung Med Univ Hosp,Kaohsiung Med Univ, Dept Emergency Med Chia Nan Univ Pharm & Sci, Dept Biotechnol Chia Nan Univ Pharm & Sci, Dept Senior Citizen Serv Management
關鍵字:	Breast cancer proteasome PSMB5 macrophage bioinformatics
日期:	2017
上傳時間:	2018-11-30 15:49:20 (UTC+8)
出版者:	E-Century Publishing Corp
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 beta 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.
關聯:	American Journal of Cancer Research, v.7, n.11, pp.2103-2120
顯示於類別:	[高齡福祉養生管理系] 期刊論文 [生物科技系(所)] 期刊論文

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