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Targeting the FOXM 1‐regulated long noncoding RNA TUG 1 in osteosarcoma
Author(s) -
Li Yang,
Zhang Tao,
Zhang Yanhui,
Zhao Xingkai,
Wang Wenbo
Publication year - 2018
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.13765
Subject(s) - osteosarcoma , downregulation and upregulation , cancer research , protein kinase b , pi3k/akt/mtor pathway , biology , signal transduction , microbiology and biotechnology , gene , biochemistry
Long noncoding RNA s (lnc RNA s) 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 TUG 1 (Taurine Upregulated Gene 1) in osteosarcoma tissues and selected it as our target for further analyses. In vitro, we found that TUG 1 was upregulated by FOXM 1 (Forkhead Box M1) in osteosarcoma cells. TUG 1 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 TUG 1 expression by upregulating the expression of FOXM 1, forming a positive feedback loop in osteosarcoma. Furthermore, we designed and synthesized therapeutic locked nucleic acids targeting TUG 1. The proliferation of osteosarcoma was significantly repressed. Hence, TUG 1 may be a potential biomarker and therapeutic target for osteosarcoma.

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