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Transcription Factors BARX1 and DLX4 Contribute to Progression of Clear Cell Renal Cell Carcinoma via Promoting Proliferation and Epithelial–Mesenchymal Transition

Authors :
Guoliang Sun
Yue Ge
Yangjun Zhang
Libin Yan
Xiaoliang Wu
Wei Ouyang
Zhize Wang
Beichen Ding
Yucong Zhang
Gongwei Long
Man Liu
Runlin Shi
Hui Zhou
Zhiqiang Chen
Zhangqun Ye
Source :
Frontiers in Molecular Biosciences, Vol 8 (2021)
Publication Year :
2021
Publisher :
Frontiers Media S.A., 2021.

Abstract

Dysregulation of transcription factors contributes to the carcinogenesis and progression of cancers. However, their roles in clear cell renal cell carcinoma remain largely unknown. This study aimed to evaluate the clinical significance of TFs and investigate their potential molecular mechanisms in ccRCC. Data were accessed from the cancer genome atlas kidney clear cell carcinoma cohort. Bioinformatics algorithm was used in copy number alterations mutations, and differentially expressed TFs’ analysis. Univariate and multivariate Cox regression analyses were performed to identify clinically significant TFs and construct a six-TF prognostic panel. TFs’ expression was validated in human tissues. Gene set enrichment analysis (GSEA) was utilized to find enriched cancer hallmark pathways. Functional experiments were conducted to verify the cancer-promoting effect of BARX homeobox 1 (BARX1) and distal-less homeobox 4 (DLX4) in ccRCC, and Western blot was performed to explore their downstream pathways. As for results, many CNAs and mutations were identified in transcription factor genes. TFs were differentially expressed in ccRCC. An applicable predictive panel of six-TF genes was constructed to predict the overall survival for ccRCC patients, and its diagnostic efficiency was evaluated by the area under the curve (AUC). BARX1 and DLX4 were associated with poor prognosis, and they could promote the proliferation and migration of ccRCC. In conclusion, the six-TF panel can be used as a prognostic biomarker for ccRCC patients. BARX1 and DLX4 play oncogenic roles in ccRCC via promoting proliferation and epithelial–mesenchymal transition. They have the potential to be novel therapeutic targets for ccRCC.

Details

Language :
English
ISSN :
2296889X
Volume :
8
Database :
Directory of Open Access Journals
Journal :
Frontiers in Molecular Biosciences
Publication Type :
Academic Journal
Accession number :
edsdoj.47a56895474d418122193516e2ee32
Document Type :
article
Full Text :
https://doi.org/10.3389/fmolb.2021.626328