Obg-like ATPase 1 (OLA1) is upregulated in the tumor tissues in different types of cancer. However, the function of OLA1 and its molecular mechanisms in endometrial cancer (EC) remain unknown. The present study aimed to elucidate OLA1 expression level and its biological function in endometrial cancer. The differential expression of OLA1 between EC tissues and non-cancerous tissues was analyzed using The Cancer Genome Atlas database and clinical samples. The association between clinicopathological characteristics and OLA1 expression was analyzed using bioinformatics analysis. Cell proliferation, migration and invasion were analyzed by short interfering RNA-mediated knockdown experiments, Cell Counting Kit-8, 5-Ethynyl-2'-deoxyuridine incorporation, wound healing, Transwell and Boyden assays. The potential signaling pathways associated with OLA1 in endometrial cancer were evaluated by Gene Set Enrichment Analysis. The expression levels of OLA1 in EC tissues were upregulated compared with that in non-cancerous tissues (P<0.001). Furthermore, patients with worse survival were found to have higher OLA1 expression, and increased OLA1 expression in endometrial cancer associated with clinical stage (P<0.01), histological type (P<0.01), histological grade (P<0.01), menstrual status (P<0.01), cancer status (P<0.05) and distant metastasis (P<0.05). In RL95-2 and HEC-1B cell lines, decreased levels of OLA1 inhibited proliferation, invasion and migration, and the TGF-β signaling pathway, ubiquitin-mediated proteolysis and Wnt signaling pathway may be involved in these mechanisms. The present study revealed that OLA1 could be a potential prognostic indicator and therapeutic target in endometrial cancer, and that the TGF-β signaling, Wnt signaling and ubiquitin-mediated proteolysis pathways may be regulated by OLA1.
Keywords: Obg-like ATPase 1; endometrial cancer; gene set enrichment analysis; prognosis; signaling pathway; the cancer genome atlas.
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