Abstract
Proline- and serine-rich 2 (PROSER2) is encoded by the 47th open reading frame on human chromosome 10. Bioinformatic analysis has shown PROSER2 was significantly correlated with prognostic outcome of osteosarcoma patients. Its role in the progression and metastasis of human osteosarcoma has not been elucidated until now. Bioinformatics analysis was performed on 101 patients with osteosarcoma from The Cancer Genome Atlas database. High levels of PROSER2 were associated with a poor prognosis in patients with osteosarcoma. PROSER2 expression was significantly upregulated in clinical specimens from patients with osteosarcoma and osteosarcoma cell lines. MTT assay was performed to test the cell viability and Transwell assay was used to test the migration and invasion of MG63 cells. PROSER2 knockdown inhibited the viability, migration and invasion of MG63 cells. Gene Set Enrichment Analysis and Gene Ontology/Kyoto Encyclopedia of Genes and Genomes analysis showed that the differentially expressed genes were primarily involved in 'calcium signaling pathway' and 'Wnt signaling' in patients with osteosarcoma and high PROSER2 expression. Western blotting analysis revealed that PROSER2 regulated migration and invasion of osteosarcoma via the Wnt/nuclear factor of activated T-cells (NFAT)c1 signaling pathway. In conclusion, PROSER2 promoted the proliferation, migration and invasion of osteosarcoma cells via the Wnt/Ca2+/NFATc1 signaling pathway by increasing nuclear localization of NFATc1.