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The circACTN4 interacts with FUBP1 to promote tumorigenesis and progression of breast cancer by regulating the expression of proto-oncogene MYC
- Source :
- Molecular Cancer, Vol 20, Iss 1, Pp 1-21 (2021), Molecular Cancer
- Publication Year :
- 2021
- Publisher :
- BMC, 2021.
-
Abstract
- Background Recent studies have revealed that circular RNAs (circRNAs) play significant roles in the occurrence and development of many kinds of cancers including breast cancer (BC). However, the potential functions of most circRNAs and the molecular mechanisms underlying progression of BC remain elusive. Method Here, Circular RNA microarray was executed in 4 pairs of breast cancer tissues and para-cancer tissues. The expression and prognostic significance of circACTN4 in BC cells and tissues were determined by qRT-PCR and in situ hybridization. Gain-and loss-of-function experiments were implemented to observe the impacts of circACTN4 on the growth, invasion, and metastasis of BC cells in vitro and in vivo. Mechanistically, chromatin immunoprecipitation, luciferase reporter, RNA pulldown, mass spectrum, RNA immunoprecipitation, fluorescence in situ hybridization and co-immunoprecipitation assays were executed. Results CircACTN4 was significantly upregulated in breast cancer tissues and cells, its expression was correlated with clinical stage and poor prognosis of patients with BC. Ectopic expression of circACTN4 strikingly facilitated the growth, invasion, and metastasis of breast cancer cells in vitro and in vivo. Whereas knockdown of circACTN4 revealed opposite roles. CircACTN4 was mainly distributed in the nucleus. Further mechanistic research proved that circACTN4 could competitively bind to far upstream element binding protein 1 (FUBP1) to prevent the combination between FUBP1 and FIR, thereby activating MYC transcription and facilitating tumor progression of breast cancer. Furthermore, we found that upstream transcription factor 2 (USF2) might promote the biogenesis of circACTN4. Conclusion Our findings uncover a pivotal mechanism that circACTN4 mediated by USF2 might interact with FUBP1 to promote the occurrence and development of breast cancer via enhancing the expression of MYC. CircACTN4 could be a novel potential target for diagnosis and treatment of breast cancer.
- Subjects :
- 0301 basic medicine
Cancer Research
Carcinogenesis
Breast Neoplasms
In situ hybridization
MYC
Biology
medicine.disease_cause
The RNA-binding protein
Metastasis
Proto-Oncogene Proteins c-myc
Mice
03 medical and health sciences
0302 clinical medicine
Breast cancer
medicine
Animals
Humans
Actinin
RC254-282
Mice, Inbred BALB C
Research
RNA-Binding Proteins
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RNA, Circular
medicine.disease
DNA-Binding Proteins
Gene Expression Regulation, Neoplastic
030104 developmental biology
Oncology
Tumor progression
030220 oncology & carcinogenesis
Disease Progression
Cancer research
Heterografts
Molecular Medicine
Oncogene MYC
Female
Ectopic expression
circactn4
FUBP1
Chromatin immunoprecipitation
Subjects
Details
- Language :
- English
- ISSN :
- 14764598
- Volume :
- 20
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Molecular Cancer
- Accession number :
- edsair.doi.dedup.....9fd7540131f73cfac1ca14f7411a90ba