Hsa_circ_0002005 aggravates osteosarcoma by increasing cell proliferation, migration, and invasion

Abstract

Emerging evidence suggests that circular RNAs (circRNAs), a class of non-coding RNAs, play a critical role in the progression of several cancers, including osteosarcoma (OS). In this study, we focused on a specific circRNA, hsa_circ_0002005, derived from the mesoderm-induced early response 1 family member 2 (MIER2) gene. We determined the expression levels of hsa_circ_0002005 in OS samples through the use of real-time quantitative polymerase chain reaction (RT-qPCR). To assess the effect of hsa_circ_0002005, we used lentiviral analysis and performed several assays including transwell migration, cell invasion, 5-ethynyl-2′-deoxyuridine assay (EdU), cell counting kit-8 (CCK-8), proliferation, colony formation, and western blotting. In addition, we investigated the delivery mechanism of hsa_circ_0002005 in nude mice and predicted the interaction network involving hsa_circ_0002005, microRNA (miRNA), and mRNAs through bioinformatics analysis. The results showed that hsa_circ_0002005 is overexpressed in OS tissues and cells and is derived from exons 2 to 7 of the MIER2 gene. Knockdown of hsa_circ_0002005 markedly reduced the proliferation, migration, and invasive capabilities of cells, as well as their metastatic potential. We discovered miRNAs that may engage with hsa_circ_0002005. Further mechanistic studies indicated that the suppression of hsa_circ_0002005 influenced the expression levels of proteins associated with the epithelial-mesenchymal transition (EMT), suggesting its regulatory role in EMT progression through modulation of cell proliferation, migration, and invasion.