Long intergenic non-coding RNA APOC1P1-3 inhibits apoptosis by decreasing α-tubulin acetylation in breast cancer.
Long intergenic non-coding RNA APOC1P1-3 inhibits apoptosis by decreasing α-tubulin acetylation in breast cancer.
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长基因间非编码 RNA APOC1P1-3 通过减少乳腺癌中的 α-微管蛋白乙酰化来抑制细胞凋亡
DOI：
10.1038/cddis.2016.142
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发表时间：
2016-05-26
影响因子：
9
通讯作者：
Zhou P
中科院分区：
文献类型：
--
作者：
Liao XH;Wang JG;Li LY;Zhou DM;Ren KH;Jin YT;Lv L;Yu JG;Yang JY;Lu Q;Zou Q;Yu J;Liu XP;Zhou P
越来越多的证据表明，长非编码RNA(LncRNAs)在肿瘤进展过程中起着重要的调节作用。然而，它们在乳腺癌中的作用在很大程度上仍不清楚。在本研究中，我们利用基因芯片技术鉴定了乳腺癌组织中异常表达的长基因间隔长非编码RNA APOC1P1-3(lincRNA-APOC1P1-3)，并通过实时定量聚合酶链式反应对其进行了验证，通过焦磷酸测序分析了启动子区域的甲基化状态。我们还通过质粒转染和siRNA沉默实验研究了它们的生物学功能，并通过RNA下拉和RNA免疫沉淀鉴定结合蛋白来进一步探讨它们的作用机制。我们发现224个lncRNAs在乳腺癌中上调，而324个在乳腺癌中下调。乳腺癌组织中lincRNA-APOC1P1-3的高表达与肿瘤大小及启动子区域的低甲基化有关。我们还发现APOC1P1-3可以直接与微管蛋白结合，从而降低α-微管蛋白的乙酰化，使其失活，并抑制细胞凋亡。本研究证明APOC1P1-3过表达可抑制乳腺癌细胞的凋亡。
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.