URG4 mediates cell proliferation and cell cycle in osteosarcoma via GSK3ß/ß-catenin/cyclin D1 signaling pathway.

BACKGROUND: Osteosarcoma is one of the most common malignant bone tumors with the annual global incidence of approximately four per million. Upregulated gene 4 (URG4) expression in the osteosarcoma tissue is closely associated with recurrence, metastasis, and poor prognosis of osteosarcoma. However, the biological function and underlying mechanisms of URG4 in osteosarcoma have not been elucidated. This study aimed to explore the expression and underlying mechanism of URG4 in osteosarcoma. METHODS: The expression level of URG4 in osteosarcoma and normal tissues was compared using immunohistochemistry (IHC). PCR and western blotting (WB) techniques are used to detect URG4 mRNA and protein levels. Wound healing and Transwell analysis to assess the effect of URG4 on osteosarcoma cell migration and invasion. Cell Counting Kit-8 assay and colony proliferation assay were performed to evaluate the effects of silencing URG4 on the inhibition of cell proliferation. The cell cycle distribution was detected by flow cytometry, and a xenograft mouse model was used to verify the function of URG4 in vivo. RESULTS: URG4 was found to be highly expressed in osteosarcoma tissues and cells, and its high expression was correlated with advanced Enneking stage, large tumor size, and tumor metastasis in osteosarcoma patients. The proliferation in osteosarcoma cell lines and cell cycle in the S phase was suppressed when siRNA was used to downregulate URG4. URG4 promoted cell proliferation and tumorigenesis in vitro and in vivo. WB verified that URG4 promotes cell proliferation in osteosarcoma via pGSK3ß/ß-catenin/cyclinD1 signaling. CONCLUSION: URG4, which is high-expressed in osteosarcoma, promotes cell cycle progression via GSK3ß/ß-catenin/cyclin D1 signaling pathway and may be a novel biomarker and potential target for the treatment of osteosarcoma.

Differential expression and bioinformatics analysis of circRNA in osteosarcoma.

AIM: This research aims to investigate the expression profile of circRNA in osteosarcoma and to identify the underlying pathogenesis core genes of osteosarcoma.Methods: Illumina HiSeq was used to screen differentially expressed circRNAs between the tumour tissues and paracancerous tissues of three osteosarcoma patients. Bioinformatics analysis was used to analyse their potential functions. Five differentially expressed circRNAs were selected to detect the relative expression level in tumour and paracancerous tissues of ten osteosarcoma patients by real-time PCR. The databases such as DisGeNET and miRWalk were used to collect related genes or miRNAs. RESULTS: A total of 259 differentially expressed circRNAs were evaluated in patients with osteosarcoma, of which 132 were up-regulated and 127 were down-regulated. Compared with that in paracancerous tissues, circ_32279 and circ_24831 were significantly down-regulated while circ_2137 and circ_20403 were significantly up-regulated in osteosarcoma tissues. The differential expression of circRNA is closely linked to biological processes and molecular functions. The difference in circRNA was mainly linked to the 'phosphatidylinositol signalling system' signal pathway and the 'inositol phosphate metabolism' signal pathway. CONCLUSION: The present study identified a profile of abnormal regulation of circRNA in osteosarcoma. Bioinformatics analysis indicates that the deregulated circRNAs may be related to the occurrence and development of osteosarcoma.