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首页> 外文期刊>Cell death & disease. >Long intergenic non-coding RNA APOC1P1-3 inhibits apoptosis by decreasing α-tubulin acetylation in breast cancer
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Long intergenic non-coding RNA APOC1P1-3 inhibits apoptosis by decreasing α-tubulin acetylation in breast cancer

机译:长基因间非编码RNA APOC1P1-3 通过降低乳腺癌中的α-微管蛋白乙酰化来抑制细胞凋亡

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Increasing evidence indicates that long non-coding RNAs (lncRNAs) act as important regulatory factors in tumor progression. However, their roles in breast cancer remain largely unknown. In present studies, we identified aberrantly expressed long intergenic non-coding RNA APOC1P1-3 ( lincRNA-APOC1P1-3) in breast cancer by microarray, verified it by quantitative real-time PCR, and assessed methylation status in the promoter region by pyrosequencing. We also investigated the biological functions with plasmid transfection and siRNA silencing experiments, and further explored their mechanisms by RNA pull-down and RNA immunoprecipitation to identify binding proteins. We found that 224 lncRNAs were upregulated in breast cancer, whereas 324 were downregulated. The lincRNA-APOC1P1-3 was overexpressed in breast cancer, which was related to tumor size and hypomethylation in its promoter region. We also found that APOC1P1-3 could directly bind to tubulin to decrease α -tubulin acetylation, to inactivate caspase-3, and to inhibit apoptosis. This study demonstrates that overexpression of APOC1P1-3 can inhibit breast cancer apoptosis.
机译:越来越多的证据表明,长的非编码RNA(lncRNA)是肿瘤进展中的重要调控因子。但是,它们在乳腺癌中的作用仍然未知。在本研究中,我们通过微阵列鉴定了在乳腺癌中异常表达的长基因间非编码RNA APOC1P1-3(lincRNA-APOC1P1-3),通过实时定量PCR进行了验证,并通过焦磷酸测序评估了启动子区域的甲基化状态。我们还通过质粒转染和siRNA沉默实验研究了生物学功能,并通过RNA下拉和RNA免疫沉淀来探索其机制以鉴定结合蛋白。我们发现在乳腺癌中有224个lncRNA上调,而有324个lncRNA下调。 lincRNA-APOC1P1-3在乳腺癌中过表达,这与肿瘤大小和启动子区域的甲基化不足有关。我们还发现,APOC1P1-3可以直接与微管蛋白结合,以减少α-微管蛋白的乙酰化,使caspase-3失活,并抑制细胞凋亡。这项研究表明,APOC1P1-3的过表达可以抑制乳腺癌的细胞凋亡。

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