Background. Previous studies had shown that lncRNA HULC exhibited different effects in human cancers. However, the role of HULC was not reported in osteosarcoma. Hence, we designed this research to explore the function of HULC in osteosarcoma. Methods. Firstly, HULC expression was measured in osteosarcoma tissues and cells via the RT-qPCR assay. The protein expression was detected through western blot. Then, CCK-8 and Transwell assays were conducted to measure cell proliferation, migration, and invasion. Results. The expression of HULC was obviously higher in osteosarcoma tissues and cells compared with normal control. Moreover, cell proliferation, migration, and invasion were inhibited by HULC knockdown in osteosarcoma cells. HULC overexpression markedly increased osteosarcoma cell proliferation and tumor size in vivo. Furthermore, HULC increased the activity of AKT-PI3K-mTOR pathway by blocking PTEN in osteosarcoma cells. LY294002 inhibited the phosphorylation of AKT, mTOR, and PI3K. Overexpressing HULC enhanced cell migration and invasion of SAOS-2 cells and MG63 cells, while LY294002 reversed the effects. Conclusion. HULC enhanced the progression of osteosarcoma through targeting PTEN.
Object. Osteosarcoma is an intractable malignant disease, and few therapeutic methods can thoroughly eradicate its focuses. This study attempted to investigate the related mechanism of osteosarcoma by bioinformatics methods. Methods. GSE70367 and GSE69470 were obtained from the GEO database. The differentially expressed genes (DEGs) and miRNAs were analyzed using the GEO2R tool and then visualized with R software. Moreover, the targets of the miRNAs in the DEGs were screened and then used for enrichment analysis. Besides, the STRING database and Cytoscape were applied to illustrate the protein-protein interaction network. RT-qPCR was performed to measure the expression of key genes and miRNAs. Western blot was applied to detect the signaling pathway. Results. 9 upregulated genes and 39 downregulated genes in GSE69470 were identified as the DEGs, and 31 upregulated genes and 56 downregulated genes in GSE70367 were identified as the DEGs. Moreover, 21 common genes were found in the DEGs of GSE70367 and GSE69470. The enrichment analysis showed that the common DEGs of GSE70367 and GSE69470 were related with cell development, covalent chromatin modification, and histone modification and involve in the regulation of MAPK, mTOR, and AMPK pathways. Besides, the miRNAs including miR-543, miR-495-3p, miR-433-3p, miR-381-3p, miR-301a-3p, miR-199b-5p, and miR-125b-5p were identified as the biomarkers of osteosarcoma. In addition, the target genes including HSPA5, PPARG, MAPK14, RAB11A, RAB5A, MAPK8, LEF1, HIF1A, CAV1, GS3KB, FOXO3, IGF1, and NFKBIA were identified as hub nodes. It was found that miR-301a-3p expression was decreased and mRNA expression of RAB5A and NFKBIA was increased in the pathological tissues. The AKT-PI3K-mTOR signaling pathway was activated in pathological tissues. Conclusion. In this study, 7 miRNAs and 13 hub genes were identified, which might be candidate markers. miR-301a-3p, RAB5A, and NFKBIA were abnormally expressed in osteosarcoma tissues.
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