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Circular RNA cia-MAF drives self-renewal and metastasis of liver tumor-initiating cells via transcription factor MAFF
- Source :
- J Clin Invest
- Publication Year :
- 2021
-
Abstract
- Liver tumor-initiating cells (TICs) are involved in liver tumorigenesis, metastasis, drug resistance and relapse, but the regulatory mechanisms of liver TICs are largely unknown. Here, we have identified a functional circular RNA, termed circRNA activating MAFF (cia-MAF), that is robustly expressed in liver cancer and liver TICs. cia-MAF knockout primary cells and cia-maf knockout liver tumors harbor decreased ratios of TICs, and display impaired liver tumorigenesis, self-renewal and metastatic capacities. In contrast, cia-MAF overexpression drives liver TIC propagation, self-renewal and metastasis. Mechanistically, cia-MAF binds to the MAFF promoter, recruits the TIP60 complex to the MAFF promoter, and finally promotes MAFF expression. Loss of cia-MAF function attenuates the combination between the TIP60 complex and the MAFF promoter. MAFF is highly expressed in liver tumors and liver TICs, and its antisense oligo (ASO) has therapeutic potential in treating liver cancer without MAFA/MAFG gene copy number alterations (CNAs). This study reveal an additional layer for liver TIC regulation as well as circRNA function, and also provide an additional target for eliminating liver TICs, especially for liver tumor without MAFA/MAFG gene CNAs.
- Subjects :
- Liver tumor
Genetic enhancement
Biology
Lysine Acetyltransferase 5
Metastasis
Mice
Circular RNA
mental disorders
medicine
Animals
Humans
MafF Transcription Factor
Copy-number variation
Cell Self Renewal
Neoplasm Metastasis
Promoter Regions, Genetic
Gene
Transcription factor
Liver Neoplasms
General Medicine
RNA, Circular
medicine.disease
Mice, Inbred C57BL
Cancer research
Neoplastic Stem Cells
Liver cancer
Research Article
Subjects
Details
- ISSN :
- 15588238
- Volume :
- 131
- Issue :
- 19
- Database :
- OpenAIRE
- Journal :
- The Journal of clinical investigation
- Accession number :
- edsair.doi.dedup.....cba07ca0b6aa19f96d6e0e773187fe7a