Screening for the presence of aberrantly expressed ACTR2 in osteosarcoma and analyzing its mechanism of action through an online database.

Abstract

Osteosarcoma (OS) represents the most prevalent malignant bone tumor clinically, significantly impacting the health and safety of patients. The exploration of molecular pathogenic mechanisms is deemed a breakthrough for OS diagnosis and treatment. Within the GSE16088 dataset, a total of 1,948 differentially expressed genes (DEGs) were identified, comprising 1,697 down-regulated and 251 up-regulated genes. Notably, only two DEGs were associated with the response to trichostatin A: ARP2 actin-related protein 2 homolog (ACTR2) and MEF2C; ACTR2 garnered particular interest. Subsequently, 57 OS patients (research group) and 50 healthy controls from the same period (control group) were selected for analysis. The expression of ACTR2 in peripheral blood in both groups, as well as its levels in cancerous tissues and adjacent counterparts of OS patients, were evaluated, ascertaining the correlation between ACTR2 and OS. OS cases exhibited lower levels of ACTR2 compared to controls (P<0.05), with ACTR2 expression demonstrating a robust diagnostic capability for OS. Similarly, ACTR2 expression was diminished in cancer tissues (P<0.05). A three-year prognostic follow-up was conducted to assess the prognostic value of ACTR2 in OS patients. The follow-up findings revealed a significantly lower survival rate among patients with low ACTR2 expression in contrast to those with high expression (P<0.05). In vitro studies involved the construction of abnormal expression vectors for ACTR2 and miR-374a-5p, which were transfected into human OS cells (U2OS, SAOS). The outcomes indicated that elevating ACTR2 or suppressing miR-374a-5p attenuated the proliferative, invasive, and migratory capacities as well as the epithelial-mesenchymal transition (EMT) of OS cells while enhancing their apoptosis. Conversely, upregulation of miR-374a-5p yielded opposing effects (P<0.05). The dual-luciferase reporter (DLR) assay demonstrated that the fluorescence activity of ACTR2-WT was significantly inhibited by the miR-374a-5p mimic sequence (P<0.05), confirming the presence of a targeted regulatory relationship between ACTR2 and miR-374a-5p. These findings offer novel insights for future research directions in the diagnosis and treatment of OS.