期刊
CANCER SCIENCE
卷 109, 期 10, 页码 3093-3104出版社
WILEY
DOI: 10.1111/cas.13765
关键词
FOXM1; miR-219a-5p; osteosarcoma; PIK3CA; TUG1
类别
资金
- Heilongjiang Provincial Academy of Medical Sciences [201715, 201814]
- Heilongjiang Provincial Ordinary Undergraduate College Young Innovative Talents Training Plan [UNPYSCT-2016111]
- Fundamental Research Funds for the Provincial Universities [2017LCZX35]
Long noncoding RNAs (lncRNAs) play an important role in the proliferation and metastasis of osteosarcoma. Identification of the pathogenesis of osteosarcoma and development of new therapeutic strategies against osteosarcoma are urgently needed. In this study, we evaluated the expression of TUG1 (Taurine Upregulated Gene 1) in osteosarcoma tissues and selected it as our target for further analyses. In vitro, we found that TUG1 was upregulated by FOXM1 (Forkhead BoxM1) in osteosarcoma cells. TUG1 accelerated osteosarcoma proliferation, migration, and invasion by competitively sponging miR-219a-5p, leading to upregulation of Phosphatidylinositol-4, 5-Bisphosphate 3-Kinase Catalytic Subunit Alpha and activation of the protein kinase B (AKT) signaling pathway. In addition, the AKT pathway activation promoted TUG1 expression by upregulating the expression of FOXM1, forming a positive feedback loop in osteosarcoma. Furthermore, we designed and synthesized therapeutic locked nucleic acids targeting TUG1. The proliferation of osteosarcoma was significantly repressed. Hence, TUG1 may be a potential biomarker and therapeutic target for osteosarcoma.
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