Prospero homeobox 1 promotes proliferation, migration, and invasion of osteosarcoma cells and its clinical significance

Abstract

ABSTRACT Osteosarcoma (OS) is the most common primary malignant bone tumor. Prospero homeobox 1 (PROX1) is a key transcription factor involved in some cancers, but the role of PROX1 in OS is unclear. This study aimed to explore the clinical and biology significance of PROX1 in OS. Fifty-four OS tissues and matched nontumor tissues were collected to explore the relationship between PROX1 expression and clinical characteristics and prognosis. qRT-PCR and immunohistochemistry were used to investigate the expression patterns of PROX1 in OS tissues and cells. CCK-8, wound healing, and transwell assays were used to detect the effects of PROX1 on the proliferation, migration, and invasion of OS cells. Transcriptome sequencing, bioinformatics analysis and qRT-PCR were used to explore the regulatory network of PROX1. PROX1 was significantly higher in OS tissues and cells compared to normal tissues and cell lines. In OS patients, high expression of PROX1 was associated with Enneking stage (P < 0.001) and M classification (P < 0.001). High PROX1 expression predicted a poorer overall survival (P = 0.0047). Compared with untreated cells, OS cells overexpressing PROX1 showed higher proliferation, migration, and invasion abilities, while knockdown of PROX1 suppressed these abilities. The results of Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis revealed that the down regulated genes were mainly enriched in TNF signaling pathway, MAPK signaling pathway, and neuroactive ligand-receptor interaction. High PROX1 expression was significantly associated with poor overall survival in OS patients. PROX1 may be a promising prognostic marker and therapeutic target for OS patients.