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LncRNA LBX2-AS1 impacts osteosarcoma sensitivity to JQ-1 by sequestering miR-597-3p away from BRD4

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单位： [1]Jiangxi Key Laboratory of Cancer Metastasis and Precision Treatment, Central Laboratory, The First Hospital of Nanchang, The Third Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China, [2]Department of Orthopedics, The First Hospital of Nanchang, The Third Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China, [3]Department of Orthopedics,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,Hubei,China

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关键词： osteosarcoma lncRNA LBX2-AS1 miR-597-3p BRD4 JQ-1

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ObjectiveRecent knowledge concerning the significance of long non-coding RNA (lncRNA)-mediated ceRNA networks provides new insight into their possible roles as specific biomarkers for the treatment of osteosarcoma (OS). Thus, this study aims to clarify the functional relevance and mechanistic actions of lncRNA LBX2-AS1 in OS. MethodsDifferential analysis was performed by integrating the TCGA and GTEx databases. Cox regression analysis was then employed to assess the prognostic value of the model. The expression of lncRNA LBX2-AS1 and miR-597-3p was quantified in OS cell lines by qRT-PCR. The proliferation, migration, invasion, and apoptosis of OS cell lines in response to manipulated lncRNA LBX2-AS1 were evaluated by MTT, colony formation, transwell, Western blot, and flow cytometry assays. Luciferase activity was assayed to validate the reciprocal regulation between lncRNA LBX2-AS1 and miR-597-3p. The protein levels of BRD4 and EMT-related factors were examined by Western blot assay. Finally, tumor growth in response to LBX2-AS1 knockdown was evaluated in xenograft-bearing nude mice. ResultsBy integrating the GTEx and TCGA databases, we identified 153 differentially expressed lncRNAs. Among them, 5 lncRNAs, RP11-535M15.1, AC002398.12, RP3-355L5.4, LBX2-AS1, and RP11.47A8.5, were selected to establish a model, which predicted the prognosis of OS. Higher lncRNA LBX2-AS1 expression was noted in OS tissues relative to that in normal tissues. Silencing lncRNA LBX2-AS1 facilitated apoptosis and curtailed proliferative, migratory, and invasive capacities of OS cells. Mechanistically, lncRNA LBX2-AS1 could elevate the expression of BRD4, an oncogene, by competitively binding to miR-597-3p. More importantly, knockdown of lncRNA LBX2-AS1 increased the sensitivity of OS cells to the BRD4 inhibitor JQ-1. Finally, the tumor growth of OS cell xenografts was constrained in vivo in the presence of lncRNA LBX2-AS1 knockdown. ConclusionIn conclusion, lncRNA LBX2-AS1 promotes the growth of OS and represses the sensitivity to JQ-1 by sponging miR-597-3p to elevate the expression of BRD4.

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出版当年[2022]版：

大类 | 3 区医学

小类 | 3 区肿瘤学

最新[2025]版：

大类 | 3 区医学

小类 | 4 区肿瘤学

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出版当年[2021]版：

Q2 ONCOLOGY

最新[2023]版：

Q2 ONCOLOGY

影响因子： 3.5 最新[2023版] 4 最新五年平均 5.738 出版当年[2021版] 6.122 出版当年五年平均 6.244 出版前一年[2020版] 4.7 出版后一年[2022版]

第一作者：

第一作者单位： [1]Jiangxi Key Laboratory of Cancer Metastasis and Precision Treatment, Central Laboratory, The First Hospital of Nanchang, The Third Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China, [2]Department of Orthopedics, The First Hospital of Nanchang, The Third Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China,

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通讯机构： [1]Jiangxi Key Laboratory of Cancer Metastasis and Precision Treatment, Central Laboratory, The First Hospital of Nanchang, The Third Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China, [2]Department of Orthopedics, The First Hospital of Nanchang, The Third Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China,

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LncRNA LBX2-AS1 impacts osteosarcoma sensitivity to JQ-1 by sequestering miR-597-3p away from BRD4

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