國家衛生研究院 NHRI:Item 3990099045/14009
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    题名: HDAC6 involves in regulating the lncRNA-microRNA-mRNA network to promote the proliferation of glioblastoma cells
    作者: Wu, AC;Yang, WB;Chang, KY;Lee, JS;Liou, JP;Su, RY;Cheng, SM;Hwang, DY;Kikkawa, U;Hsu, TI;Wang, CY;Chang, WC;Chen, PY;Chuang, JY
    贡献者: National Institute of Cancer Research
    摘要: BACKGROUND: Glioblastoma (GBM) is the most aggressive and lethal brain tumor. Although the histone deacetylase (HDAC)/transcription factor axis promotes growth in GBM, whether HDACs including HDAC6 are involved in modulating long non-coding RNAs (lncRNAs) to affect GBM malignancy remains obscure. METHODS: Integrative analysis of microarray and RNA-seq was performed to identify lncRNAs governed by HDAC6. Half-life measurement and RNA-protein pull-down assay combined with isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomic analysis were conducted to identify RNA modulators. The effect of LINC00461 on GBM malignancy was evaluated using animal models and cell proliferation-related assays. Functional analysis of the LINC00461 downstream networks was performed comprehensively using ingenuity pathway analysis and public databases. RESULTS: We identified a lncRNA, LINC00461, which was substantially increased in stem-like/treatment-resistant GBM cells. LINC00461 was inversely correlated with the survival of mice-bearing GBM and it was stabilized by the interaction between HDAC6 and RNA-binding proteins (RBPs) such as carbon catabolite repression-negative on TATA-less (CCR4-NOT) core exoribonuclease subunit 6 and fused in sarcoma. Targeting LINC00461 using azaindolylsulfonamide, an HDAC6 inhibitor, decreased cell-division-related proteins via the lncRNA-microRNA (miRNA)-mRNA networks and caused cell-cycle arrest, thereby suppressing proliferation in parental and drug-resistant GBM cells and prolonging the survival of mice-bearing GBM. CONCLUSIONS: This study sheds light on the role of LINC00461 in GBM malignancy and provides a novel therapeutic strategy for targeting the HDAC6/RBP/LINC00461 axis and its downstream effectors in patients with GBM.
    日期: 2022-02-02
    關聯: Journal of Experimental and Clinical Cancer Research. 2022 Feb 2;41:Article number 47.
    Link to: http://dx.doi.org/10.1186/s13046-022-02257-w
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1756-9966&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000750170600001
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85123974394
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