Browsing by Subject "BRD4"

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    Circ_0000376 downregulation inhibits the progression of non-small cell lung cancer by mediating the miR-488-3p/BRD4 axis and the PI3K/PKB signaling pathway
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2021) Yuan, Hongmei; Wu, Hongge; Cheng, Jing; Xiong, Jie
    Background. The involvement of circular RNAs (circRNAs) in the development of cancers has attracted much interest. This study aimed to determine the role of circ_0000376 in non-small cell lung cancer (NSCLC) and provide a new mechanism. Methods. The expression of circ_0000376, miR488-3p and bromodomain containing 4 (BRD4) mRNA was measured by quantitative real-time PCR (qPCR). Cell behaviors, including cell proliferation, invasion, migration, apoptosis and cell cycle progression were investigated using cell counting kit-8 (CCK-8) assay and colony formation assay, transwell assay, wound healing assay and flow cytometry assay, respectively. The putative relationship between miR-488-3p and circ_0000376 or BRD4 was verified by dual-luciferase reporter assay. The protein levels of BRD4 and phosphorylated PI3K/PKB were detected by western blot. Xenograft model was constructed to determine the role of circ_0000376 in vivo. Results. Circ_0000376 was highly expressed in NSCLC tissues and cells. Circ_0000376 downregulation inhibited NSCLC cell proliferation, invasion and migration, promoted cell apoptosis and cell cycle arrest and slowed tumor growth in vivo. Circ_0000376 competitively bound to miR-488-3p to regulate the expression of BRD4. Rescue experiments showed that miR-488-3p deficiency reversed the effects of circ_0000376 downregulation, and miR-488-3p restoration-suppressed cell proliferation, migration and invasion were recovered by BRD4 overexpression. Moreover, circ_0000376 downregulation weakened the levels of phosphorylated PI3K and PKB, thus reducing the activity of the PI3K/PKB pathway. Conclusion. Circ_0000376 downregulation blocked the development of NSCLC by targeting the miR-488- 3p/BRD4 network and suppressing the PI3K/PKB pathway, which broadens knowledge into the understanding of the role of circ_0000376 in NSCLC.
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    CircKCNQ5 controls proliferation, migration, invasion, apoptosis, and glycolysis of multiple myeloma cells by modulating miR-335-5p/BRD4 axis
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Li, Yan; Wang, Liang; Zhang, Nan; Xu, Yan
    Background. Circular RNAs (circRNAs) are key players in tumorigenesis progression. However, the role and molecular mechanisms of circKCNQ5 in multiple myeloma (MM) progression remain unclear. Methods. The quantitative real-time polymerase chain reaction was used for examining circKCNQ5, miR-335-5p, and Bromodomain-containing protein 4 (BRD4) levels. The proliferation ability of MM cells was determined by Cell Counting Kit-8 and colonyforming assays. The migration and invasion were analyzed by transwell assay. Flow cytometry was used to assess cell apoptosis. The lactate production, glucose consumption, and ATP/ADP ratios were determined by commercialized kits. The protein levels were quantified by western blot analysis. The interactions between circKCNQ5 and miR-335-5p, along with miR-335-5p and BRD4 were analyzed by dual-luciferase reporter and RNA immunoprecipitation assays. Results. The overexpression of circKCNQ5 was confirmed in MM tissues and cells. Importantly, knockdown of circKCNQ5 suppressed proliferation, migration, invasion, and glycolysis while it increased apoptosis of MM cells in vitro. Interestingly, the downregulation of miR-335-5p was able to rescue the circKCNQ5 inhibition-induced effects on MM cells. MiR-335-5p interacted with circKCNQ5, and was able to target BRD4 in MM cells. MiR-335-5p upregulation inhibited malignant phenotypes of MM cells depending on BRD4. Conclusion. CircKCNQ5 was found to stimulate MM progression through competitively sponging to miR-335-5p.
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    The BRD4 inhibitor JQ1 protects against chronic obstructive pulmonary disease in mice by suppressing NF-κB activation
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2021) Liu, Yan; Huang, Zhi Zhen; Min, Li; Li, Zhi Feng; Chen, Kui
    Objective. To examine the effect of the BRD4 inhibitor JQ1 on mice with chronic obstructive pulmonary disease (COPD) via NF-κB. Methods. COPD models constructed by exposure to cigarette smoke and intratracheal instillation of lipopolysaccharides (LPS) in mice were treated with JQ1 (15, 25 or 50 mg/kg). HE staining was performed to observe histopathological changes in the lung tissues. Enzyme-linked immunosorbent assays (ELISAs) were used to measure the levels of IL-10, IFN-γ, IL-17, IL1β, IL-6, TNF-α, MMP-2, MMP-9, MDA, SOD, T-AOC and HO-1, and gelatin zymography assays were used to examine MMP-2 and MMP-9 activity. A TransAMTM NF-κB p65 detection kit was used to test NF-κB p65/DNA binding activity. Western blotting was conducted to analyze NF-κB p65 in the nucleus and its acetylation. Results. JQ1 dose-dependently improved the histopathological changes in the lung tissues and decreased the mean linear intercept (MLI), destructive index and inflammatory score of the mice with COPD. The mice with COPD showed increased levels of MMP2, MMP-9, IFN-γ, IL-17, IL-1β, IL-6 and TNF-α with decreased IL-10 level; these changes were reversed by JQ1 in a dose-dependent manner. In addition, JQ1 reduced the MDA level and increased the SOD, HO-1 and T-AOC levels in mice with COPD, with suppression of NF-κB p65 expression in the nucleus, NF-κB/p65 (Lys310) acetylation and NF-κB p65/DNA binding activity in the lung tissues. Conclusion. The BRD4 inhibitor JQ1 can downregulate MMP-2 and MMP-9 expression, reduce inflammatory responses, and alleviate oxidative stress in mice with COPD, and this mechanism might be related to the inhibition of NF-κB.