Dataset Information

Long noncoding RNA UCA1 promotes osteosarcoma metastasis through CREB1-mediated epithelial-mesenchymal transition and activating PI3K/AKT/mTOR pathway.

ABSTRACT: Increasing evidences have demonstrated that Long noncoding RNAs (lncRNAs) are key regulatory RNAs that participate in multiple biological processes. LncRNA urothelial carcinoma-associated 1 (UCA1) is a newly identified lncRNA and functions as a regulator of growth in several cancers. However, the biological function and molecular mechanism of UCA1 in the metastasis of osteosarcoma remain unclear. In this study, we firstly found UCA1 is upregulated in both osteosarcoma tissues and cell lines, and increased UCA1 is associated with higher tumor stage, larger tumor size and poorer prognosis. Then for the first time, we demonstrated that UCA1 promotes the invasion and metastasis of osteosarcoma both in vitro and in vivo. Further mechanistic investigation showed that UCA1 directly interactes with miR-582 and suppresses its expression. Moreover, UCA1 increases CREB1 expression by functioning as a ceRNA against miR-582, thus promoting the EMT process via CREB1-mediated PI3K/AKT/mTOR pathway and finally leading to osteosarcoma metastasis. These findings may extend the function of UCA1 in osteosarcoma progression and provide a promising therapeutic target for osteosarcoma treatment.

SUBMITTER: Ma H

PROVIDER: S-EPMC6463206 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Long noncoding RNA UCA1 promotes osteosarcoma metastasis through CREB1-mediated epithelial-mesenchymal transition and activating PI3K/AKT/mTOR pathway.

Ma Hangzhan H Su Rujuan R Feng Hongwei H Guo Yongliang Y Su Gengxun G

Journal of bone oncology 20190301

Increasing evidences have demonstrated that Long noncoding RNAs (lncRNAs) are key regulatory RNAs that participate in multiple biological processes. LncRNA urothelial carcinoma-associated 1 (UCA1) is a newly identified lncRNA and functions as a regulator of growth in several cancers. However, the biological function and molecular mechanism of UCA1 in the metastasis of osteosarcoma remain unclear. In this study, we firstly found UCA1 is upregulated in both osteosarcoma tissue ...[more]

PMID: 31011522

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Project description:PurposeNectin-4 is specifically up-regulated in various tumors, exert crucial effects on tumor occurrence and development. Nevertheless, the role and molecular mechanism of Nectin-4 in osteosarcoma (OS) are rarely studied.MethodsThe expression of Nectin-4 and its relationship with clinical characteristics of OS were investigated using OS clinical tissues, tissue microarrays, TCGA, and GEO databases. Moreover, the effect of Nectin-4 on cell growth and mobility was detected by CCK-8, colony formation, transwell, and wound-healing assays. The RT-qPCR, Western blotting, and luciferase reporter assays were performed to explore molecular mechanisms through which Nectin-4 mediates the expression of miR-520c-3p, thus modulating PI3K/AKT/NF-κB signaling. In vivo mice models constructed by subcutaneous transplantation and tail vein injection were used to validate the functional roles of Nectin-4 and miR-520c-3p.ResultsNectin-4 displayed a higher expression in OS tumor tissues compared with normal tissues, and its overexpression was positively associated with tumor stage and metastasis in OS patients. Functionally, Nectin-4 enhanced OS cells growth and mobility in vitro. Mechanistically, Nectin-4 down-regulated the levels of miR-520c-3p that directly targeted AKT-1 and P65, thus leading to the stimulation of PI3K/AKT/NF-κB signaling. In addition, the expression of miR-520c-3p was apparently lower in OS tissues than in normal tissues, and its low expression was significantly related to tumor metastasis. Furthermore, ectopic expression of miR-520c-3p markedly blocked the effect of Nectin-4 on OS cell growth and mobility. Knockdown of Nectin-4 could suppress the tumorigenesis and metastasis in vivo, which could be remarkably reversed by miR-520c-3p silencing.ConclusionsNectin-4 as an oncogene can promote OS progression and metastasis by activating PI3K/AKT/NF-κB signaling via down-regulation of miR-520c-3p, which could represent a novel avenue for identifying a potential therapeutic target for improving patient outcomes.

Dataset Information

Long noncoding RNA UCA1 promotes osteosarcoma metastasis through CREB1-mediated epithelial-mesenchymal transition and activating PI3K/AKT/mTOR pathway.

Publications

Long noncoding RNA UCA1 promotes osteosarcoma metastasis through CREB1-mediated epithelial-mesenchymal transition and activating PI3K/AKT/mTOR pathway.

Similar Datasets

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