title: A novel cellular senescence gene, SENEX, is involved in peripheral regulatory T cells accumulation in aged urinary bladder cancer.
abstract: Regulatory T cells (Tregs) play an essential role in sustaining self-tolerance and immune homeostasis. Despite many studies on the correlation between Tregs accumulation and age, or malignancies, the related mechanism hasn't been well explored. To find out the mechanism of Tregs accumulation in aged urinary bladder cancer, we examined the novel cellular senesence gene SENEX and relevant apoptosis gene mRNA expression in sorted CD4+CD25(hi) Tregs from aged UBC donors, evaluated serum cytokine profiles related to tumor immunopathology, and further explored the relationship between SENEX expression, apoptosis gene expression and cytokine secretion. After having silenced down SENEX gene expression with RNA interference, we also evaluated the cellular apoptosis of Tregs sorted from aged UBC patients in response to H₂O₂-mediated stress. Our data indicated that upregulated SENEX mRNA expression in Tregs of aged UBC patients was correlated with pro-apoptotic gene expression and cytokine concentration. Silencing SENEX gene expression increased cellular apoptosis and pro-apoptotic gene expression of Tregs, in response to H₂O₂-mediated stress. Upregulated SENEX mRNA expression together with decreased pro-apoptotic gene expression and disturbances in cytokines synthesis may contribute to the Tregs proliferation and promote tumorigenesis and metastasis. Overall, upregulation of cellular senescence gene SENEX, was associated to regulatory T cells accumulation in aged urinary bladder cancer. Our study provides a new insight into understanding of peripheral Tregs accumulation in aged malignancies.
authors: Department of Hematology, Second Hospital of Anhui Medical University, Hefei, China ; Hematology Research Centre, Second Hospital of Anhui Medical University, Hefei, China.
authors: Tianping
authors: T
authors: Chen
authors: Department of Hematology, Second Hospital of Anhui Medical University, Hefei, China ; Hematology Research Centre, Second Hospital of Anhui Medical University, Hefei, China.
authors: Huiping
authors: H
authors: Wang
authors: Department of Urology, Second Hospital of Anhui Medical University, Hefei, China.
authors: Zhiqiang
authors: Z
authors: Zhang
authors: Central Laboratory, Anhui Provincial Hospital, Hefei, China.
authors: Qing
authors: Q
authors: Li
authors: Department of Hematology, Second Hospital of Anhui Medical University, Hefei, China.
authors: Kaili
authors: K
authors: Yan
authors: Department of Hematology, Second Hospital of Anhui Medical University, Hefei, China.
authors: Qianshan
authors: Q
authors: Tao
authors: Department of Hematology, Second Hospital of Anhui Medical University, Hefei, China ; National Institutes of Health and WESTMEAD Transplants and Kidney Disease Research Centre, Sydney University, Sydney, Australia.
authors: Qianling
authors: Q
authors: Ye
authors: Department of Hematology, Second Hospital of Anhui Medical University, Hefei, China ; Hematology Research Centre, Second Hospital of Anhui Medical University, Hefei, China.
authors: Shudao
authors: S
authors: Xiong
authors: National Institutes of Health and WESTMEAD Transplants and Kidney Disease Research Centre, Sydney University, Sydney, Australia.
authors: Yiping
authors: Y
authors: Wang
authors: Department of Hematology, Second Hospital of Anhui Medical University, Hefei, China ; Hematology Research Centre, Second Hospital of Anhui Medical University, Hefei, China.
authors: Zhimin
authors: Z
authors: Zhai
mesh_terms: D000368:Aged; D016922:Cellular Senescence / Q000235:genetics / Q000276:immunology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000276:immunology; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000276:immunology; D012334:RNA, Neoplasm / Q000096:biosynthesis* / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D001749:Urinary Bladder Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
chemical_list: D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm