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circCHST15 is a novel prognostic biomarker that promotes clear cell renal cell carcinoma cell proliferation and metastasis through the miR-125a-5p/EIF4EBP1 axis
- Source :
- Molecular Cancer, Molecular Cancer, Vol 20, Iss 1, Pp 1-21 (2021)
- Publication Year :
- 2021
-
Abstract
- Background Circular RNAs (circRNAs) have been indicated as potentially critical mediators in various types of tumor progression, generally acting as microRNA (miRNA) sponges to regulate downstream gene expression. However, the aberrant expression profile and dysfunction of circRNAs in human clear cell renal cell carcinoma (ccRCC) need to be further investigated. This study mined key prognostic circRNAs and elucidates the potential role and molecular mechanism of circRNAs in regulating the proliferation and metastasis of ccRCC. Methods circCHST15 (hsa_circ_0020303) was identified by mining two circRNA microarrays from the Gene Expression Omnibus database and comparing matched tumor versus adjacent normal epithelial tissue pairs or matched primary versus metastatic tumor tissue pairs. These results were validated by quantitative real-time polymerase chain reaction and agarose gel electrophoresis. We demonstrated the biological effect of circCHST15 in ccRCC both in vitro and in vivo. To test the interaction between circCHST15 and miRNAs, we conducted a number of experiments, including RNA pull down assay, dual-luciferase reporter assay and fluorescence in situ hybridization. Results The expression of circCHST15 was higher in ccRCC tissues compared to healthy adjacent kidney tissue and higher in RCC cell lines compared to normal kidney cell lines. The level of circCHST15 was positively correlated with aggressive clinicopathological characteristics, and circCHST15 served as an independent prognostic indicator for overall survival and progression-free survival in patients with ccRCC after surgical resection. Our in vivo and in vitro data indicate that circCHST15 promotes the proliferation, migration, and invasion of ccRCC cells. Mechanistically, we found that circCHST15 directly interacts with miR-125a-5p and acts as a microRNA sponge to regulate EIF4EBP1 expression. Conclusions We found that sponging of miR-125a-5p to promote EIF4EBP1 expression is the underlying mechanism of hsa_circ_0020303-induced ccRCC progression. This prompts further investigation of circCHST15 as a potential prognostic biomarker and therapeutic target for ccRCC.
- Subjects :
- Adult
Male
Clear cell renal cell carcinoma
Cancer Research
Proliferation
Cell Cycle Proteins
miR-125a-5p
Models, Biological
Metastasis
Mice
Cell Line, Tumor
Biomarkers, Tumor
Animals
Humans
Carcinoma, Renal Cell
RC254-282
Adaptor Proteins, Signal Transducing
Aged
Neoplasm Staging
EIF4EBP1
Membrane Glycoproteins
Research
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RNA, Circular
Middle Aged
Prognosis
Kidney Neoplasms
Gene Expression Regulation, Neoplastic
Disease Models, Animal
MicroRNAs
Oncology
hsa_circ_0020303
Molecular Medicine
Heterografts
Female
RNA Interference
Neoplasm Grading
Sulfotransferases
Subjects
Details
- ISSN :
- 14764598
- Volume :
- 20
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Molecular cancer
- Accession number :
- edsair.doi.dedup.....7934a5b4e8c372609099841082384411