MafF Is Regulated via the circ-ITCH/miR-224-5p Axis and Acts as a Tumor Suppressor in Hepatocellular Carcinoma.

Abstract

MafF is a member of the basic leucine zipper (bZIP) transcription factor Maf family and is commonly downregulated in multiple cancers. But the expression and function of MafF in hepatocellular carcinoma (HCC) remain unclear. In this study, we investigated the relationship between endogenous MafF expression and HCC progression and explored the regulatory mechanism of MafF expression in HCC. We found that MafF decreased in HCC tissues and cells. Lentivirus-mediated MafF overexpression inhibited HCC cell proliferation and induced cell apoptosis. Bioinformatics analysis and luciferase assay identified MafF as a direct target of miR-224-5p. RNA pull-down assay demonstrated that circular RNA circ-ITCH could sponge miR-224-5p specifically in HCC. The rescue experiments further elucidated that the expression and antitumor effects of MafF could be regulated via the circ-ITCH/miR-224-5p axis. This study verified that MafF acted as a tumor suppressor in HCC and revealed the upstream regulation mechanism of MafF, which provided a new perspective for potential therapeutic targets of HCC.

• Authors: Minhua Wu, Xubin Deng, Yu Zhong, Li Hu, Xiujuan Zhang, Yanqin Liang, Xiaofang Li, Xiaoxia Ye
• Journal: Oncology research (Oncol Res) Vol. 28 Issue 3 Pg. 299-309 (May 29 2020) ISSN: 1555-3906 [Electronic] United States
• PMID: 31969212 (Publication Type: Journal Article)

Chemical References

• MAFF protein, human
• MIRN224 microRNA, human
• MafF Transcription Factor
• MicroRNAs
• Nuclear Proteins
• RNA, Circular
• Repressor Proteins
• ITCH protein, human
• Ubiquitin-Protein Ligases

Topics

• Apoptosis (genetics)
• Carcinoma, Hepatocellular (genetics, metabolism, pathology)
• Cell Line, Tumor
• Cell Movement
• Cell Proliferation
• Gene Expression Regulation, Neoplastic
• Humans
• Liver Neoplasms (genetics, metabolism, pathology)
• MafF Transcription Factor (metabolism)
• MicroRNAs (genetics)
• Nuclear Proteins (metabolism)
• RNA Interference
• RNA, Circular
• Repressor Proteins (genetics)
• Ubiquitin-Protein Ligases (genetics)