MicroRNA-455-3p inhibits osteosarcoma progression via HSF1 downregulation

Abstract

ObjectiveThis study was conducted to dissect the role and potential mechanism of microRNA (miR)-455-3p on osteosarcoma (OS) development. MethodsmiR-455-3p and HSF1 expression in OS tissues were detected by RT-qPCR and western blot. Later, gain- and loss-of-function assays were implemented in OS cells U–2OS and MNNG. The expression of apoptosis-related genes was measured by RT-qPCR and western blot. MTT, Transwell, scratch test, and flow cytometry were utilized to test OS cell viability, invasion, migration, and apoptosis. The targeting relationship between miR-455-3p and HSF1 was assessed with a dual-luciferase reporter gene assay. The transplantation tumor experiment in nude mice was utilized for in vivo confirmation. ResultsDownregulated miR-455-3p and upregulated HSF1 were displayed in OS tissues and cells. Mechanistically, miR-455-3p negatively targeted HSF1. MiR-455-3p inhibition or HSF1 overexpression increased MNNG and U–2OS cell proliferative, invasive, and migrating capabilities, while diminishing U–2OS cell apoptosis. Moreover, HSF1 overexpression negated the impacts of miR-455-3p upregulation on OS cell proliferative, invasive, migrating, and apoptotic abilities. Likewise, overexpressing miR-455-3p curtailed the growth of transplanted OS tumors through HSF1 repression. ConclusionMiR-455-3p inhibits the development of OS cells by downregulating HSF1, highlighting the possibility of miR-455-3p as an innovative indicator of prognosis and a therapeutic target for OS.