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FMR1/circCHAF1A/miR-211-5p/HOXC8 feedback loop regulates proliferation and tumorigenesis via MDM2-dependent p53 signaling in GSCs
- Source :
- Oncogene. 40:4094-4110
- Publication Year :
- 2021
- Publisher :
- Springer Science and Business Media LLC, 2021.
-
Abstract
- Glioma is the most common and fatal primary malignant brain tumor. Glioma stem cells (GSCs) may be an important factor in glioma cell proliferation, invasion, chemoradiotherapy tolerance, and recurrence. Therefore, discovering novel GSCs related circular RNAs (circRNAs) may finds out a prospective target for the treatment of glioma. A novel circRNA-CHAF1A (circCHAF1A) was first found in our study. CircCHAF1A was overexpressed in glioma and related to the low survival rate. Functionally, it was found that no matter in vitro or in vivo, circCHAF1A can facilitate the proliferation and tumorigenesis of TP53wt GSCs. Mechanistically, circCHAF1A upregulated transcription factor HOXC8 expression in GSCs through miR-211-5p sponging. Then, HOXC8 can transcriptionally upregulate MDM2 expression and inhibited the antitumor effect of p53. Furtherly, the RNA binding protein FMR1 can bind to and promoted the expression of circCHAF1A via maintaining its stability, while HOXC8 also transcribed the FMR1 expression to form a feedback loop, which may be involved in the malignant transformation of glioma. The novel feedback loop among FMR1, circCHAF1A, miR-211-5p, and HOXC8 in GSCs can facilitate the proliferation and tumorigenesis of glioma and GSCs. It also provided a helpful biomarker for diagnosis and prognostic evaluation of glioma and may be applied to molecular targeted therapy.
- Subjects :
- 0301 basic medicine
Cancer Research
Carcinogenesis
medicine.medical_treatment
Apoptosis
medicine.disease_cause
Targeted therapy
Malignant transformation
Fragile X Mental Retardation Protein
Mice
0302 clinical medicine
Cell Movement
Prospective Studies
Mice, Inbred BALB C
Brain Neoplasms
Proto-Oncogene Proteins c-mdm2
Glioma
Prognosis
Up-Regulation
Gene Expression Regulation, Neoplastic
030220 oncology & carcinogenesis
Mdm2
Female
Stem cell
Signal Transduction
Mice, Nude
Biology
Feedback
03 medical and health sciences
Downregulation and upregulation
Cell Line, Tumor
Genetics
medicine
Animals
Humans
Molecular Biology
Transcription factor
Cell Proliferation
Homeodomain Proteins
fungi
RNA, Circular
medicine.disease
nervous system diseases
MicroRNAs
030104 developmental biology
Cancer research
biology.protein
Tumor Suppressor Protein p53
Subjects
Details
- ISSN :
- 14765594 and 09509232
- Volume :
- 40
- Database :
- OpenAIRE
- Journal :
- Oncogene
- Accession number :
- edsair.doi.dedup.....58b394b358584e38376d6b93ef1bcccf