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

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.

A zinc finger protein gene signature enables bladder cancer treatment stratification

“…Our results showed that ZNF350 expression was associated with reduced BC risk, which is consistent with previous results [ 24 ]. Similarly, another report associated high expression levels of ZNF195 with favorable survival in BC [ 25 ]. In contrast, the roles of ZNRD1, APEX2, and EBF4 in BC onset and development had not, to our knowledge, been as yet explored.…”

Identification of a novel signature based on unfolded protein response-related gene for predicting prognosis in bladder cancer

“…Studies have confirmed the critical function of HSPB6 in the endothelial proliferation and migration of various cancers [ 35 , 36 ]. Overexpression of HSPB6 suppressed BLCA T24 cell migration to a certain level but had no effect on T24 cell proliferation [ 37 ]. F-box protein 6 (FBXO6), a vital component of the ubiquitin protein ligase complex, has been reported to be involved in the invasion and sensitivity of cisplatin [ 38 ].…”

Screening and Identification of Novel Potential Biomarkers for Breast Cancer Brain Metastases

“…SPANX family encompasses cancer-testis antigens that are epigenetically silenced in normal tissue except testes, while expressed in several human tumors (116,117). SPANXB1 has been reported to be expressed in melanoma and carcinomas of breast, lung, ovary, colon, and bladder (118)(119)(120). In TNBC, SPANXB1 has been shown to promote lung and liver metastasis and be traceable in the circulating extracellular vesicles (120).…”