Evaluating the biological functions of the prognostic genes identified by the Pathology Atlas in bladder cancer.
Oncol Rep
; 45(1): 191-201, 2021 01.
Article
in En
| MEDLINE
| ID: mdl-33200223
ABSTRACT
The prognosisassociated 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 survivalassociated 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, MITdomain containing protein 1 (MITD1) transfection was demonstrated to inhibit T24 cell migration to a certain degree. Experiments performed with a 7gene 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 migrationassociated 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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Urinary Bladder Neoplasms
/
Membrane Proteins
/
Microtubule-Associated Proteins
Type of study:
Prognostic_studies
Limits:
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
Oncol Rep
Journal subject:
NEOPLASIAS
Year:
2021
Document type:
Article