LHX2 promotes malignancy and inhibits autophagy via mTOR in osteosarcoma and is negatively regulated by miR-129-5p
Identifieur interne : 000699 ( Main/Exploration ); précédent : 000698; suivant : 000700LHX2 promotes malignancy and inhibits autophagy via mTOR in osteosarcoma and is negatively regulated by miR-129-5p
Auteurs : Honghai Song [République populaire de Chine] ; Jiaming Liu [République populaire de Chine] ; Xin Wu [République populaire de Chine] ; Yang Zhou [République populaire de Chine] ; Xuanyin Chen [République populaire de Chine] ; Jiangwei Chen [République populaire de Chine] ; Keyu Deng [République populaire de Chine] ; Chunxia Mao [République populaire de Chine] ; Shanhu Huang [République populaire de Chine] ; Zhili Liu [République populaire de Chine]Source :
- Aging (Albany NY) [ 1945-4589 ] ; 2019.
Abstract
The transcript factor LHX2 is dysregulated in many cancers but its role in osteosarcoma (OS) remains unclear. In this study, we confirm that LHX2 is up-regulated in osteosarcoma, and that its silencing inhibits OS malignancy and induces autophagy via mTOR signaling. We further demonstrate that miR-129-5p negatively regulates LHX2 and suppresses the malignant phenotypes of OS. LHX2 overexpression could restore the malignant phenotypes. In conclusion, LHX2 regulates tumorigenesis and autophagy via mTOR in OS and is negatively regulated by miR-129-5p. Targeting the miR-129-5p/LHX2/mTOR axis therefore represents a novel therapeutic strategy for OS treatment.
Url:
DOI: 10.18632/aging.102427
PubMed: 31724536
PubMed Central: 6874432
Affiliations:
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330006</wicri:noRegion></affiliation></author><author><name sortKey="Chen, Jiangwei" sort="Chen, Jiangwei" uniqKey="Chen J" first="Jiangwei" last="Chen">Jiangwei Chen</name><affiliation wicri:level="1"><nlm:aff id="aff2">Department of Orthopedic Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Orthopedic Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006</wicri:regionArea><wicri:noRegion>Jiangxi 330006</wicri:noRegion></affiliation></author><author><name sortKey="Deng, Keyu" sort="Deng, Keyu" uniqKey="Deng K" first="Keyu" last="Deng">Keyu Deng</name><affiliation wicri:level="1"><nlm:aff id="aff4">The National Engineering Research Center for Bioengineering Drugs and Technologies, Institute of Translational Medicine, Nanchang University, Nanchang, Jiangxi 330031, China</nlm:aff><country 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330031</wicri:noRegion></affiliation></author><author><name sortKey="Huang, Shanhu" sort="Huang, Shanhu" uniqKey="Huang S" first="Shanhu" last="Huang">Shanhu Huang</name><affiliation wicri:level="1"><nlm:aff id="aff2">Department of Orthopedic Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Orthopedic Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006</wicri:regionArea><wicri:noRegion>Jiangxi 330006</wicri:noRegion></affiliation></author><author><name sortKey="Liu, Zhili" sort="Liu, Zhili" uniqKey="Liu Z" first="Zhili" last="Liu">Zhili Liu</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Science and Technology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China</nlm:aff><country xml:lang="fr">République populaire de 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sort="Song, Honghai" uniqKey="Song H" first="Honghai" last="Song">Honghai Song</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Science and Technology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Science and Technology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006</wicri:regionArea><wicri:noRegion>Jiangxi 330006</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2">Department of Orthopedic Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Orthopedic Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006</wicri:regionArea><wicri:noRegion>Jiangxi 330006</wicri:noRegion></affiliation></author><author><name sortKey="Liu, Jiaming" sort="Liu, Jiaming" uniqKey="Liu J" first="Jiaming" last="Liu">Jiaming Liu</name><affiliation wicri:level="1"><nlm:aff id="aff2">Department of Orthopedic Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Orthopedic Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006</wicri:regionArea><wicri:noRegion>Jiangxi 330006</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff3">Jiangxi Institute of Respiratory Disease, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Jiangxi Institute of Respiratory Disease, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006</wicri:regionArea><wicri:noRegion>Jiangxi 330006</wicri:noRegion></affiliation></author><author><name sortKey="Wu, Xin" sort="Wu, Xin" uniqKey="Wu X" first="Xin" last="Wu">Xin Wu</name><affiliation wicri:level="1"><nlm:aff id="aff2">Department of Orthopedic Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Orthopedic Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006</wicri:regionArea><wicri:noRegion>Jiangxi 330006</wicri:noRegion></affiliation></author><author><name sortKey="Zhou, Yang" sort="Zhou, Yang" uniqKey="Zhou Y" first="Yang" last="Zhou">Yang Zhou</name><affiliation wicri:level="1"><nlm:aff id="aff2">Department of Orthopedic Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Orthopedic Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006</wicri:regionArea><wicri:noRegion>Jiangxi 330006</wicri:noRegion></affiliation></author><author><name sortKey="Chen, Xuanyin" sort="Chen, Xuanyin" uniqKey="Chen X" first="Xuanyin" last="Chen">Xuanyin Chen</name><affiliation wicri:level="1"><nlm:aff id="aff2">Department of Orthopedic Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Orthopedic Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006</wicri:regionArea><wicri:noRegion>Jiangxi 330006</wicri:noRegion></affiliation></author><author><name sortKey="Chen, Jiangwei" sort="Chen, Jiangwei" uniqKey="Chen J" first="Jiangwei" last="Chen">Jiangwei Chen</name><affiliation wicri:level="1"><nlm:aff id="aff2">Department of Orthopedic Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Orthopedic Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006</wicri:regionArea><wicri:noRegion>Jiangxi 330006</wicri:noRegion></affiliation></author><author><name sortKey="Deng, Keyu" sort="Deng, Keyu" uniqKey="Deng K" first="Keyu" last="Deng">Keyu Deng</name><affiliation wicri:level="1"><nlm:aff id="aff4">The National Engineering Research Center for Bioengineering Drugs and Technologies, Institute of Translational Medicine, Nanchang University, Nanchang, Jiangxi 330031, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>The National Engineering Research Center for Bioengineering Drugs and Technologies, Institute of Translational Medicine, Nanchang University, Nanchang, Jiangxi 330031</wicri:regionArea><wicri:noRegion>Jiangxi 330031</wicri:noRegion></affiliation></author><author><name sortKey="Mao, Chunxia" sort="Mao, Chunxia" uniqKey="Mao C" first="Chunxia" last="Mao">Chunxia Mao</name><affiliation wicri:level="1"><nlm:aff id="aff4">The National Engineering Research Center for Bioengineering Drugs and Technologies, Institute of Translational Medicine, Nanchang University, Nanchang, Jiangxi 330031, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>The National Engineering Research Center for Bioengineering Drugs and Technologies, Institute of Translational Medicine, Nanchang University, Nanchang, Jiangxi 330031</wicri:regionArea><wicri:noRegion>Jiangxi 330031</wicri:noRegion></affiliation></author><author><name sortKey="Huang, Shanhu" sort="Huang, Shanhu" uniqKey="Huang S" first="Shanhu" last="Huang">Shanhu Huang</name><affiliation wicri:level="1"><nlm:aff id="aff2">Department of Orthopedic Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Orthopedic Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006</wicri:regionArea><wicri:noRegion>Jiangxi 330006</wicri:noRegion></affiliation></author><author><name sortKey="Liu, Zhili" sort="Liu, Zhili" uniqKey="Liu Z" first="Zhili" last="Liu">Zhili Liu</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Science and Technology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Science and Technology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006</wicri:regionArea><wicri:noRegion>Jiangxi 330006</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2">Department of Orthopedic Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Orthopedic Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006</wicri:regionArea><wicri:noRegion>Jiangxi 330006</wicri:noRegion></affiliation></author></analytic><series><title level="j">Aging (Albany NY)</title><idno type="eISSN">1945-4589</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>The transcript factor LHX2 is dysregulated in many cancers but its role in osteosarcoma (OS) remains unclear. In this study, we confirm that LHX2 is up-regulated in osteosarcoma, and that its silencing inhibits OS malignancy and induces autophagy via mTOR signaling. We further demonstrate that miR-129-5p negatively regulates LHX2 and suppresses the malignant phenotypes of OS. LHX2 overexpression could restore the malignant phenotypes. In conclusion, LHX2 regulates tumorigenesis and autophagy via mTOR in OS and is negatively regulated by miR-129-5p. Targeting the miR-129-5p/LHX2/mTOR axis therefore represents a novel therapeutic strategy for OS treatment.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>République populaire de Chine</li></country></list><tree><country name="République populaire de Chine"><noRegion><name sortKey="Song, Honghai" sort="Song, Honghai" uniqKey="Song H" first="Honghai" last="Song">Honghai Song</name></noRegion><name sortKey="Chen, Jiangwei" sort="Chen, Jiangwei" uniqKey="Chen J" first="Jiangwei" last="Chen">Jiangwei Chen</name><name sortKey="Chen, Xuanyin" sort="Chen, Xuanyin" uniqKey="Chen X" first="Xuanyin" last="Chen">Xuanyin Chen</name><name sortKey="Deng, Keyu" sort="Deng, Keyu" uniqKey="Deng K" first="Keyu" last="Deng">Keyu Deng</name><name sortKey="Huang, Shanhu" sort="Huang, Shanhu" uniqKey="Huang S" first="Shanhu" last="Huang">Shanhu Huang</name><name sortKey="Liu, Jiaming" sort="Liu, Jiaming" uniqKey="Liu J" first="Jiaming" last="Liu">Jiaming Liu</name><name sortKey="Liu, Jiaming" sort="Liu, Jiaming" uniqKey="Liu J" first="Jiaming" last="Liu">Jiaming Liu</name><name sortKey="Liu, Zhili" sort="Liu, Zhili" uniqKey="Liu Z" first="Zhili" last="Liu">Zhili Liu</name><name sortKey="Liu, Zhili" sort="Liu, Zhili" uniqKey="Liu Z" first="Zhili" last="Liu">Zhili Liu</name><name sortKey="Mao, Chunxia" sort="Mao, Chunxia" uniqKey="Mao C" first="Chunxia" last="Mao">Chunxia Mao</name><name sortKey="Song, Honghai" sort="Song, Honghai" uniqKey="Song H" first="Honghai" last="Song">Honghai Song</name><name sortKey="Wu, Xin" sort="Wu, Xin" uniqKey="Wu X" first="Xin" last="Wu">Xin Wu</name><name sortKey="Zhou, Yang" sort="Zhou, Yang" uniqKey="Zhou Y" first="Yang" last="Zhou">Yang Zhou</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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