Knockdown of long noncoding RNA CCDC144NL-AS1 attenuates migration and invasion phenotypes in endometrial stromal cells from endometriosis
Knockdown of long noncoding RNA CCDC144NL-AS1 attenuates migration and invasion phenotypes in endometrial stromal cells from endometriosis
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长链非编码RNA CCDC144NL-AS1的敲低可减弱子宫内膜异位症引起的子宫内膜基质细胞的迁移和侵袭表型
DOI：
10.1093/biolre/ioy252
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发表时间：
2018
影响因子：
3.6
通讯作者：
Xiaohong Chang
中科院分区：
文献类型：
--
作者：
Chen Zhang;Wei Wu;Honglan Zhu;Xiaoming Yu;Yinli Zhang;Xue Ye;Hongyan Cheng;Ruiqiong Ma;Heng Cui;Jianjun Luo;Jing Guan;Xiaohong Chang
子宫内膜异位症（EM）是一种多因素引起的神秘而复杂的疾病。近年来的研究表明，长链非编码RNA（lncRNA）在EM的发病机制中起重要作用。然而，lncRNA在EM中的功能和生物学机制仍然未知。在这里，我们进行了微阵列分析，比较四对异位子宫内膜（EC）组织和在位子宫内膜（EU）组织的卵巢EM患者的lncRNA表达谱。一种新的lncRNA CCDC 144 NL-AS 1被鉴定为具有潜在的功能。与EU和正常子宫内膜（NE）组织相比，EC组织中CCDC 144 NL-AS 1表达上调。86.7%（26/30）的EM患者EC组织中表达高于EU组织。尽管根据修订的美国生育学会（rAFS）分期没有显著增加，但约60%的VI期EM病例显示出更高的CCDC 144 NL-AS 1水平，比II-III期病例高得多。亚细胞分级显示CCDC 144 NL-AS 1定位于人EM来源的永生化子宫内膜间质细胞系hEM 15 A的细胞质和细胞核中。CCDC 144 NL-AS 1缺失可抑制hEM 15 A细胞的迁移和侵袭能力，但对细胞的粘附、增殖、凋亡和细胞周期无影响。与阴性对照组处理相比，CCDC 144 NL-AS 1的敲除显著改变了细胞骨架丝状肌动蛋白（F-肌动蛋白）应力纤维的分布。Western blot分析显示CCDC 144 NL-AS 1的敲低降低了波形蛋白丝和MMP-9的蛋白水平，但不降低N-钙粘蛋白和β-连环蛋白的蛋白水平。综上所述，我们的研究结果表明CCDC 144 NL-AS 1可能参与了EM的发病机制，并为卵巢EM提供了一个新的靶点。
Endometriosis (EM) is a mysterious and complicated disease that has been found to be multifactorial. Recent studies demonstrated that long noncoding RNAs (lncRNAs) play an important role in the pathogenesis of EM. However, the functional and biological mechanisms of lncRNAs in EM remain unknown. Here, we performed microarray analyses to compare the lncRNA expression profiles of four paired ectopic endometrial (EC) tissues and eutopic endometrial (EU) tissues from patients with ovarian EM. A novel lncRNA, CCDC144NL-AS1, was identified as being potentially functional. CCDC144NL-AS1 expression was upregulated in EC tissues compared to EU and normal endometrial (NE) tissues. Its expression was higher in EC tissues than in EU tissues in 86.7% (26/30) of patients with EM. Despite the lack of a significant increase according to revised American Fertility Society (rAFS) stages, approximately 60% of stage VI EM cases exhibited higher CCDC144NL-AS1 levels, many more than in the stage II–III cases. Subcellular fractionation demonstrated that CCDC144NL-AS1 was localized in the cytoplasm and nucleus of the human EM-derived immortalized endometrial stromal cell line hEM15A. CCDC144NL-AS1 depletion suppressed the migration and invasion of hEM15A cells, but exerted no effects on cell adhesion, proliferation, apoptosis, or cell cycle. Knockdown of CCDC144NL-AS1 dramatically altered the distribution of cytoskeletal filamentous actin (F-actin) stress fibers compared to the negative control group treatment. Western blot analysis revealed that knockdown of CCDC144NL-AS1 attenuated the protein levels of vimentin filaments and MMP-9, but not N-cadherin or β-catenin. Collectively, our results suggest that CCDC144NL-AS1 might be involved in the pathogenesis of EM and provide a novel target for ovarian EM.