Bioinformatics Analysis Identifies ASCL1 as the Key Transcription Factor in Hepatocellular Carcinoma Progression.

Abstract

Methods: Differentially transcription factors (DETFs) were identified from differentially expressed genes (DEGs) in GSE62232 and transcription factors. Then, they were analyzed by regulatory networks, prognostic risk model, and overall survival analyses to identify the key DETF. Combined with the regulatory networks and binding site analysis, the target mRNA of key DETF was determined, and its prognostic value in HCC was evaluated by survival, clinical characteristics analyses, and experiments. Finally, the expressions and functions of the key DETF on the DEmRNAs were investigated in HCC cells.

Results: Through multiple bioinformatics analyses, ASCL1 was identified as the key DETF, and SLC6A13 was predicted to be its target mRNA with the common binding site of CCAGCAACTGGCC, both downregulated in HCC. In survival analysis, high SLC6A13 was related to better HCC prognosis, and SLC6A13 was differentially expressed in HCC patients with clinical characteristics. Furthermore, cell experiments showed the mRNA expressions of ASCL1 and SLC6A13 were both reduced in HCC, and their overexpressions suppressed the growth, invasion, and migration of HCC cells. Besides, over-ASCL1 could upregulate SLC6A13 expression in HCC cells.

Conclusion: This study identifies two suppressor genes in HCC progression, ASCL1 and SLC6A13, and the key transcription factor ASCL1 suppresses HCC progression by targeting SLC6A13 mRNA. They are both potential treatment targets and prognostic biomarkers for HCC patients, which provides new clues for HCC research.