Aberrant expression of CHL1 gene and long non-coding RNA CHL1-AS1, CHL1-AS2 in ovarian endometriosis
Aberrant expression of CHL1 gene and long non-coding RNA CHL1-AS1, CHL1-AS2 in ovarian endometriosis
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CHL1基因及长链非编码RNA CHL1-AS1、CHL1-AS2在卵巢子宫内膜异位症中的异常表达
DOI：
10.1016/j.ejogrb.2019.03.020
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发表时间：
2019-05-01
影响因子：
2.6
通讯作者：
Chang, Xiaohong
中科院分区：
文献类型：
--
作者：
Zhang, Chen;Wu, Wei;Chang, Xiaohong
目的(S)：CHL1(L1或细胞黏附分子L1样同源)，又称CALL，是神经细胞黏附分子L1基因家族的成员，属于免疫球蛋白超家族。本研究旨在探讨CHL1基因与CHL1-AS1和CHL1-AS2长非编码RNA(IncRNAs)的潜在相关性，并验证CHL1和CHL1-AS2在卵巢子宫内膜异位症(EM)中的表达模式。研究设计：我们先前对4例卵巢EM患者进行的微阵列分析(GSE86534)表明，与在位内膜(EU)组织相比，CHL1是异位内膜(EC)中表达最高的mRNA，其两个反义IncRNAs CHL1-AS1和CHL1-AS2的表达模式相同。我们使用基于生物信息学的策略来计算CHL1、CHL-AS1和CHL1-AS2之间的相关性。基因集浓缩分析(GSEA)分析CHL1-AS1和CHL1-AS2常见的富集组基因。应用实时定量聚合酶链式反应(QPCR)检测了30例EM患者的EC和EU配对组织及27例正常子宫内膜(NE)组织中CHL1mRNA和IncRNACHL1-AS2的表达水平。结果：CHL1、CHL1-AS1和CHL1-AS2三者之间存在显著的相关性，生物信息学计算的Pearson相关系数为>；0.9。GSEA结果显示，CHL1-AS1和CHL1-AS2与同一基因集合“WAMUNYOKOLI_OVOVICE_CORCER_LMP”呈负相关。定量聚合酶链式反应证实CHL1和CHL1-AS2在EC组织中的表达水平显著高于EU和NE组织，而EU和NE组织中CHL1和CHL1-AS2的表达水平无显著差异。食管癌组织中ChL1和ChL1AS2的相对表达水平与EU组织相比呈显著正相关(P=0.421.0 2，P=0.0 2)。Western blotting检测到EC组织中CHL1蛋白表达升高。结论：CHL1、CHL1-AS1和CHL1-AS2三者之间存在显著的相关性，可能参与了卵巢内膜异位症的发生发展，有望成为进一步研究的新靶点。(C)2019爱思唯尔B.V.保留所有权利。
Objective(s): CHL1 (close homologue of L1 or cell adhesion molecule L1 like), also referred as CALL, is a member of the L1 gene family of neural cell adhesion molecules and belongs to immunoglobulin superfamily. This study aims to investigate the potential correlation of the CHL1 gene and the long noncoding RNAs (IncRNAs), i.e., CHL1-AS1 and CHL1-AS2, and to validate the expression patterns of CHL1 and CHL1-AS2 in ovarian endometriosis (EM).Study design: Our previous microarray analyses (GSE86534) of 4 patients with ovarian EM indicated that CHL1 was the most upregulated mRNA in ectopic endometrium (EC) compared with eutopic endometrium (EU) tissues, and that its two antisense IncRNAs CHL1-AS1 and CHL1-AS2, exhibited the same expression pattern. We used a bioinformatics-based strategy to calculate the correlation among CHL1, CHL-AS1 and CHL1-AS2. Gene set enrichment analysis (GSEA) was performed to analyze commonly enriched gene sets for CHL1-AS1 and CHL1-AS2. Using quantitative real-time polymerase chain reaction (qPCR), we examined the expression levels of CHL1 mRNA and IncRNA CHL1-AS2 in paired tissues of EC and EU from 30 EM patients and normal endometrium (NE) tissues from 27 controls using quantitative real-time polymerase chain reaction (qPCR). We also examined the expression of CHL1 protein in EC, EU and NE tissues using western blotting and immunohistochemistry (IHC).Results: CHL1, CHL1-AS1 and CHL1-AS2 were significantly correlated with each other given that the Pearson correlation values were > 0.9 using bioinformatic calculation. GSEA revealed that CHL1-AS1 and CHL1-AS2 were negatively associated with the same gene set "WAMUNYOKOLI_OVARIAN_CANCER_LMP". qPCR confirmed that the CHL1 and CHL1-AS2 expression levels were significantly higher in EC tissues than in EU and NE tissues, while they were not significantly different in EU compared with NE tissues. The relative expression levels of CHL1 and CHL1-AS2 in EC compared with EU tissues were positively significantly correlated (Pearson correlation coefficient = 0.421 and P value = 0.02). Elevated expression of CHL1 protein in EC tissues was detected by western blotting. IHC revealed that CHL1 protein expression levels enhanced in ectopic endometrial glands and stroma.Conclusion(s): Our results indicate a significant correlation among CHL1, CHL1-AS1 and CHL1-AS2, which might be involved in the development of ovarian EM and serve as novel targets for future research. (C) 2019 Elsevier B.V. All rights reserved.