Hsa_circ_0004296 inhibits metastasis of prostate cancer by interacting with EIF4A3 to prevent nuclear export of ETS1 mRNA

作者：Shiyu Mao, Wentao Zhang, Fuhan Yang, Yadong Guo, Hong Wang, Yuan Wu, Ruiliang Wang, Niraj Maskey, Zongtai Zheng, Li Cheng, Wenchao Ma, Junfeng Zhang, Yan Yang, Xudong Yao · 发表于：Journal of Experimental & Clinical Cancer Research · 年份：2021 · DOI：10.1186/s13046-021-02138-8 · 被引用次数：49 · 研究领域：Circular RNAs in diseases、Connective Tissue Growth Factor Research、Cancer-related molecular mechanisms research

BACKGROUND: Circular RNAs (circRNAs) have been shown to play vital biological functions in various tumors, including prostate cancer (PCa). However, the roles of circRNAs in the metastasis of PCa remain unclear. In the present study, differentially expressed circRNAs associated with PCa metastasis were screened using high-throughput RNA sequencing, from which hsa_circ_0004296 was identified. 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 confirm...