Abstract
Liver metastasis of colorectal cancer (CRC) is a major cause of cancer morbidity and mortality. Circular RNAs (circRNAs) have been widely reported to be implicated in cancer metastasis. This study aims to investigate the effect of circSP5 (has_circ_0057010) on liver metastasis of CRC. Quantitative real-time PCR (RT-qPCR) analysis was performed to detect gene expression. The level of proteins was measured by western blot. The migration and invasion of CRC cells were assessed by wound healing assay and transwell assay. In vivo assays were performed after the construction of the CRC xenograft model and CRC model with liver metastasis. Mechanism analyses were performed via RNA-binding protein immunoprecipitation (RIP), RNA pulldown, luciferase reporter, chromatin immunoprecipitation (ChIP), and DNA pulldown assays. We found that circSP5 is significantly overexpressed in CRC with liver metastasis and its depletion suppresses the progression of CRC with liver metastasis in vitro and in vivo. Moreover, circSP5 enhances the expression of Sp5 transcription factor (SP5) via competitively sponging microRNA (miR)-1249-3p and could regulate BMP and activin membrane-bound inhibitor (BAMBI) via transcriptional activation. CircSP5 promotes the migration, invasion, and epithelial-mesenchymal transition (EMT) of CRC cells via BAMBI. In sum, circSP5 promotes liver metastasis of CRC by up-regulating SP5-mediated BAMBI transcription.
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Acknowledgements
We thank all our experimenters for their efforts.
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This work was supported by the National Natural Science Foundation of China (No. 82103439).
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Study concept and design: Yingru Zhi and Qingyuan Gao. Acquisition of data: Jie Yuan and Zhenyu Zhang. Analysis and interpretation of data: Yingru Zhi and Zhenyu Zhang. Drafting of the manuscript: Yingru Zhi. Critical revision of the manuscript for important intellectual content: Zhenyu Zhang. Statistical analysis: Zhibing Wang, Yu Dong, and Yue Guan. Study supervision: Jie Yuan.
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Zhi, Y., Gao, Q., Wang, Z. et al. Circular RNA circSP5 promotes liver metastasis of colorectal cancer via SP5-mediated BAMBI transcription. Funct Integr Genomics 23, 275 (2023). https://doi.org/10.1007/s10142-023-01142-9
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DOI: https://doi.org/10.1007/s10142-023-01142-9