CircAkt3 participates in bone cancer pain progression in rats by modulating MAPK signalling pathway

Abstract

Abstract Background: Cancer-induced bone paincaused by advanced tumor bone metastasis remains a clinical challenge, and the underlying mechanisms of BCP remain unknown. This study aimed to screen the expression profile of circular RNAs in a BCP rat model and provide a new theoretical basis for the role of circular RNA in the occurrence and development of BCP. Methods: We established a BCP rat model. The top four differentially expressed circRNAs (DECs) in the model were validated by agarose gel electrophoresis and Sanger sequencing between the BCP group and sham group. A circRNA-miRNA-mRNA network was constructed based on the interactions among circRNAs, microRNA (miRNA), and mRNA, which were predicted by TargetScan. mRNA and circRNA expression levels were detected by quantitative RT-PCR. In addition, Western Blot was performed to identify the protein levels of p-ERK, ERK, and Col8a1. Results: CircRNA parent genes were mainly enriched in MAPK and neurodevelopmental signalling pathways. CircAkt3 and circMap4k1 were significantly up-regulated in the BCP group. CircaAkt3 may increase p-ERK expression by upregulating Col8a1, which may further activate the MAPK pathway. Conclusions: The circAkt3 pathway may influence the development of bone cancer pain by activating the MAPK signaling pathway. This study provided important targets for the development of therapeutic strategy against BCP.