ELK1-induced upregulation of long non-coding RNA MIR100HG predicts poor prognosis and promotes the progression of osteosarcoma by epigenetically silencing LATS1 and LATS2 - 09/12/18
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Graphical abstract |
Highlights |
• | MIR100HG was overexpressed in OS tissues and cell lines and predicted poor prognosis for OS patients. |
• | Knockdown of MIR100HG inhibited OS progression by affecting cell proliferation, cell cycle distribution and cell apoptosis. |
• | MIR100HG inactivated Hippo pathway by epigenetically silencing LATS1/2. |
Abstract |
Osteosarcoma (OS) is the commonest malignant bone tumor in the world. High incidence of OS has gradually become a social problem. Recent years, numerous studies have revealed that long non-coding RNAs (lncRNAs) are crucial regulators in the tumor progression. As a member of lncRNA family, MIR100HG has been reported to be an oncogene in breast cancer and acute megakaryoblastic leukemia. Nevertheless, the specific role of MIR100HG in osteosarcoma is still unclear. In this study, we investigated the biological function and molecular mechanism of MIR100HG in the progression of osteosarcoma. At first, we measured the high expression of MIR100HG in OS tissues and cell lines by qRT-PCR. Kaplan-Meier method revealed that high expression of MIR100HG is a factor for the poor prognosis of OS patients (P = 0.004). To explore the effect of MIR100HG on the biological processes of OS, loss-of-function assays were conducted in OS cells. Functionally, MIR100HG knockdown suppressed cell proliferation, cell cycle progression while promoted cell apoptosis. Mechanistically, MIR100HG was upregulated by the transcription factor ELK1. The upregulation of MIR100HG led to the inactivation of Hippo pathway. Furthermore, we found that MIR100HG inactivated Hippo pathway in OS cells by epigenetically silencing LATS1 and LATS2. Rescue assays demonstrated that LATS1/2 involved in MIR100HG-mediated OS progression. In summary, our study indicated that ELK1-induced upregulation of MIR100HG promoted OS progression by epigenetically silencing LATS1 and LATS2 and inactivating Hippo pathway.
Le texte complet de cet article est disponible en PDF.Keywords : MIR100HG, ELK1, Hippo signaling pathway, Proliferation, Osteosarcoma
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Vol 109
P. 788-797 - janvier 2019 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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