Abstract | BACKGROUND: RESULTS: Immunohistochemical staining showed that FLI1 is aberrantly overexpressed in advanced stage and metastatic breast cancers. Using a CRISPR Cas9-guided immunoprecipitation assay, we identify a circular RNA in the FLI1 promoter chromatin complex, consisting of FLI1 exons 4-2-3, referred to as FECR1.Overexpression of FECR1 enhances invasiveness of MDA-MB231 breast cancer cells. Notably, FECR1 utilizes a positive feedback mechanism to activate FLI1 by inducing DNA hypomethylation in CpG islands of the promoter. FECR1 binds to the FLI1 promoter in cis and recruits TET1, a demethylase that is actively involved in DNA demethylation. FECR1 also binds to and downregulates in trans DNMT1, a methyltransferase that is essential for the maintenance of DNA methylation. CONCLUSIONS:
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Authors | Naifei Chen, Gang Zhao, Xu Yan, Zheng Lv, Hongmei Yin, Shilin Zhang, Wei Song, Xueli Li, Lingyu Li, Zhonghua Du, Lin Jia, Lei Zhou, Wei Li, Andrew R Hoffman, Ji-Fan Hu, Jiuwei Cui |
Journal | Genome biology
(Genome Biol)
Vol. 19
Issue 1
Pg. 218
(12 11 2018)
ISSN: 1474-760X [Electronic] England |
PMID | 30537986
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
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Chemical References |
- FLI1 protein, human
- MAS1 protein, human
- Proto-Oncogene Mas
- Proto-Oncogene Protein c-fli-1
- Proto-Oncogene Proteins
- Mixed Function Oxygenases
- TET1 protein, human
- DNA (Cytosine-5-)-Methyltransferase 1
- DNMT1 protein, human
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Topics |
- Breast Neoplasms
(metabolism)
- CRISPR-Cas Systems
- DNA (Cytosine-5-)-Methyltransferase 1
(metabolism)
- DNA Methylation
- Gene Expression Regulation, Neoplastic
- Humans
- Mixed Function Oxygenases
(metabolism)
- Neoplasm Metastasis
- Proto-Oncogene Mas
- Proto-Oncogene Protein c-fli-1
(metabolism)
- Proto-Oncogene Proteins
(metabolism)
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