PLAC8 Facilitates Osteosarcoma Growth and Metastasis by Upregulating CXCL5 Expression via miR-363-3p

Background: Placenta-associated 8 protein (PLAC8) has been documented to play a role in tumorigenesis and tumor progression in various malignancies. However, there is still limited understanding of its function in Osteosarcoma (OS). This study aimed to analyze the potential effects and understand the underlying molecular mechanism of PLAC8 in OS.Methods: The expression patterns of PLAC8 were investigated in OS cell lines and clinical tissue samples. The effects of PLAC8 on cell proliferation and movement were assessed by Cell Counting Kit-8 (CCK-8), colony formation, Transwell (R), and woundhealing assays. Additionally, qRT-PCR, Western blotting, and luciferase reporter assays were performed to examine the expression and explore the molecular mechanisms behind PLAC8. Finally, to further determine the effect of PLAC8 in vivo, tumorigenesis and metastasis assays were employed in a mouse xenograft tumor model.Results: The current study revealed that PLAC8 was significantly overexpressed in clinical OS samples (p < 0.01) and in indicated cell lines (p < 0.05). In vitro experiments uncovered that PLAC8 could enhance the proliferative and metastatic probability of OS (p < 0.05). In addition, PLAC8 knockdown attenuated OS tumorigenesis in vivo. Moreover, PLAC8 was positively associated with the levels of C-X-C motif chemokine ligand 5 (CXCL5) in osteosarcoma, and PLAC8 overexpression upregulated CXCL5 mRNA (p < 0.01) and protein (p < 0.05). Mechanistically, microRNA-363-3p (miR-363-3p), suppressed by PLAC8, could directly target CXCL5 mRNA, leading to a decrease in CXCL5. Functionally, rescue and blocking assays validated that PLAC8 could promote the growth and mobility of osteosarcoma cells by releasing the targeting of CXCL5 by miR-363-3p.Conclusions: In summary, the oncogenic role of PLAC8 contributed to the development of osteosarcoma by mediating the miR363-3p/CXCL5 axis. The finding may serve as a valuable reference for precise treatment and therapeutic development in osteosarcoma.