Evaluating the biological functions of the prognostic genes identified by the Pathology Atlas in bladder cancer

Chen,Yuanbin; Chen,Yuanbin; Chen,Yuanbin; Chen,Yuanbin; Xu,Ting; Xu,Ting; Xu,Ting; Xu,Ting; Xie,Fei; Xie,Fei; Xie,Fei; Xie,Fei; Wang,Liping; Wang,Liping; Wang,Liping; Wang,Liping; Liang,Zhijuan; Liang,Zhijuan; Liang,Zhijuan; Liang,Zhijuan; Li,Dan; Li,Dan; Li,Dan; Li,Dan; Liang,Ye; Liang,Ye; Liang,Ye; Liang,Ye; Zhao,Kaidong; Zhao,Kaidong; Zhao,Kaidong; Zhao,Kaidong; Qi,Xiangjie; Qi,Xiangjie; Qi,Xiangjie; Qi,Xiangjie; Yang,Xuecheng; Yang,Xuecheng; Yang,Xuecheng; Yang,Xuecheng; Jiao,Wei; Jiao,Wei; Jiao,Wei; Jiao,Wei

doi:10.3892/or.2020.7853

Evaluating the biological functions of the prognostic genes identified by the Pathology Atlas in bladder cancer

Authors:
- Yuanbin Chen
- Ting Xu
- Fei Xie
- Liping Wang
- Zhijuan Liang
- Dan Li
- Ye Liang
- Kaidong Zhao
- Xiangjie Qi
- Xuecheng Yang
- Wei Jiao
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Affiliations: Department of Urology, The Affiliated Hospital of Qingdao University, Qingdao 266003, P.R. China, Department of Geratology, The 971th Hospital of PLA Navy, Qingdao 266000, P.R. China, Department of Urology, People's Hospital of Linzi District, Zibo, Shandong 255400, P.R. China
Published online on: November 13, 2020 https://doi.org/10.3892/or.2020.7853
Pages: 191-201
Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The prognosis‑associated genes of urinary bladder cancer have been systematically investigated in the Pathology Atlas project based on The Cancer Genome Atlas data. However, the biological functions of most genes in bladder cancer remain unknown. The present study investigated the biological function of 12 of the most significant survival‑associated genes (ABRACL, MITD1, ZNF524, EMP1, HSPB6, CXorf38, TRIM38, ZNF182, ZNF195, SPRN, PTPN6 and LIPT1) in urothelial cancer reported by the Pathology Atlas project, with respect to cell proliferation and migration. In vitro, proliferation and migration analyses of T24 cells were performed following the transfection of the 12 prognostic genes. The results were validated with a small interfering (si)RNA library. Immunohistochemistry (IHC) analysis of clinical samples was performed to determine the association between gene expression and tumor metastasis. Furthermore, RNA sequencing was used to investigate the downstream signals. Among the 12 prognostic genes, MIT‑domain containing protein 1 (MITD1) transfection was demonstrated to inhibit T24 cell migration to a certain degree. Experiments performed with a 7‑gene siRNA library demonstrated that MITD1 knockdown markedly upregulated cell migratory abilities. Mechanistically, the influence of MITD1 on cell signal transduction was assessed via RNA sequencing. Cell migration‑associated genes, including KISS1, SPANXB1, SPINT1, PIWIL2, SNAI1, APLN and CTHRC1 were dysregulated. IHC analysis demonstrated that MITD1 protein expression was notably lower in metastatic lymph nodes compared with the primary tumors. Taken together, the results of the present study suggest that the prognostic gene, MITD1 may serve as a migration inhibitor, and be developed as a potential therapeutic target for improving the prognosis of bladder cancer.

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