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image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao The Journal of Gene ...arrow_drop_down
image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
The Journal of Gene Medicine
Article . 2021 . Peer-reviewed
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Down‐regulation of circITCH promotes osteosarcoma development and resistance to doxorubicin via the miR‐524/RASSF6 axis

Authors: Wei Zhou; Yuan Liu; Xuejian Wu;

Down‐regulation of circITCH promotes osteosarcoma development and resistance to doxorubicin via the miR‐524/RASSF6 axis

Abstract

AbstractBackgroundOsteosarcoma (OS) is a malignant bone cancer, in which circular RNAs (circRNAs) act as important modulators. The present study aimed to explore the functional role of circRNA itchy E3 ubiquitin protein ligase (circITCH) in the development and doxorubicin (DXR) resistance of OS and the possible mechanistic pathway.MethodsA quantitative real‐time polymerase chain reaction or western blot assays were exploited to analyze the expression of circITCH, miR‐524 and Ras association domain family member 6 (RASSF6). Cell viability and half‐maximal inhibitory concentration (IC50) value of DXR were monitored using a cell counting kit‐8 assay. Cell migration, invasion and apoptosis were determined via a transwell assay and flow cytometry. The target interaction among circITCH, miR‐524 and RASSF6 was validated by dual‐luciferase reporter and RNA immunoprecipitation assays. A xenograft model of MG‐63/DXR cells stably expressing circITCH in nude mice was established for assessing the role of circITCH in vivo.ResultsDown‐regulation of circITCH and RASSF6, as well as the up‐regulation of miR‐524, was revealed in OS by investigating 40 paired OS tissue and normal tissue samples. Overexpression of circITCH lowered the cell viability, IC50 value of DXR, migration and invasion, whereas it facilitated apoptosis of OS cells. circITCH sponged miR‐524 to up‐regulate RASSF6, causing OS progression inhibition and DXR resistance reduction. Additionally, circITCH up‐regulation reduced tumor growth in vivo.ConclusionsTransduction with circITCH represses OS progression and promotes DXR sensitivity by the miR‐524/RASSF6 axis, providing a new perspective for therapeutic intervention.

Related Organizations
Subjects by Vocabulary

Microsoft Academic Graph classification: Flow cytometry Downregulation and upregulation In vivo medicine Doxorubicin Viability assay medicine.diagnostic_test Chemistry Cell migration medicine.disease Apoptosis Cancer research Osteosarcoma medicine.drug

Keywords

Male, Cell Survival, Down-Regulation, Mice, Nude, Apoptosis, Bone Neoplasms, Mice, Cell Movement, Cell Line, Tumor, Drug Discovery, Genetics, Animals, Humans, Molecular Biology, Genetics (clinical), Cell Proliferation, Mice, Inbred BALB C, Osteosarcoma, RNA, Circular, Up-Regulation, Gene Expression Regulation, Neoplastic, MicroRNAs, Doxorubicin, Drug Resistance, Neoplasm, Molecular Medicine, Apoptosis Regulatory Proteins

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  • citations
    This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    10
    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Top 10%
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    Average
    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Top 10%
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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
10
Top 10%
Average
Top 10%
bronze