Abstract | BACKGROUND: METHODS: Quantitative real-time PCR (qRT-PCR) was used to detect the expression of circ_0004296 in PCa tissues and adjacent normal tissues as well as in blood and urine. Gain and loss of function experiments were performed to investigate the function of circ_0004296 in PCa. Bioinformatics analyses, RNA pull-down assay, and mass spectrometry were conducted to identify RNA-binding proteins. RNA immunoprecipitation and RNA and protein nuclear-cytoplasmic fractionation were performed to investigate the underlying mechanism. A xenograft mouse model was used to analyze the effect of circ_0004296 on PCa growth and metastasis in vivo. RESULTS: The expression of circ_0004296 was decreased in PCa tissues, blood, and urine, which was negatively associated with metastasis. Furthermore, gain and loss of function experiments in vitro and in vivo showed that circ_0004296 inhibited the proliferation, migration, invasion, and epithelial-mesenchymal transition of PCa cells. Mechanistically, circ_0004296 regulated host gene ETS1 expression at the post-transcriptional level. EIF4A3 was identified and confirmed as the downstream binding protein of circ_0004296. EIF4A3 expression was significantly upregulated in PCa tissues and associated with PCa metastasis. Silencing EIF4A3 suppressed PCa cell proliferation, migration, invasion, and EMT. CONCLUSIONS: Circ_0004296 overexpression efficiently inhibited ETS1 mRNA nuclear export by promoting EIF4A3 retention in the nucleus, leading to the downregulation of ETS1 expression and suppression of PCa metastasis; thus, circ_0004296 might be a potential biomarker and therapeutic target for patients with PCa.
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Authors | Shiyu Mao, Wentao Zhang, Fuhan Yang, Yadong Guo, Hong Wang, Yuan Wu, Ruiliang Wang, Niraj Maskey, Zongtai Zheng, Cheng Li, Wenchao Ma, Junfeng Zhang, Yang Yan, Xudong Yao |
Journal | Journal of experimental & clinical cancer research : CR
(J Exp Clin Cancer Res)
Vol. 40
Issue 1
Pg. 336
(Oct 25 2021)
ISSN: 1756-9966 [Electronic] England |
PMID | 34696782
(Publication Type: Journal Article)
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Copyright | © 2021. The Author(s). |
Chemical References |
- ETS1 protein, human
- Proto-Oncogene Protein c-ets-1
- RNA, Circular
- RNA, Messenger
- Eukaryotic Initiation Factor-4A
- EIF4A3 protein, human
- DEAD-box RNA Helicases
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Topics |
- Active Transport, Cell Nucleus
- Animals
- Cell Line, Tumor
- Cell Movement
- Computational Biology
(methods)
- DEAD-box RNA Helicases
(genetics, metabolism)
- Disease Models, Animal
- Eukaryotic Initiation Factor-4A
(genetics, metabolism)
- Gene Expression Profiling
- Gene Expression Regulation, Neoplastic
- Gene Knockdown Techniques
- Heterografts
- Humans
- Male
- Mice
- Models, Biological
- Prostatic Neoplasms
(genetics, metabolism, pathology)
- Protein Binding
- Proto-Oncogene Protein c-ets-1
(genetics)
- RNA, Circular
(genetics)
- RNA, Messenger
(genetics, metabolism)
- Transcriptome
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