长非编码 RNA 与 Syncytin-1/Syncytin-2 基因和转录本的相互作用：非编码 RNA 如何影响系统性红斑狼疮患者的妊娠

Interaction between Long Noncoding RNAs and Syncytin-1/Syncytin-2 Genes and Transcripts: How Noncoding RNAs May Affect Pregnancy in Patients with Systemic Lupus Erythematosus.

机构信息

Rheumatology Unit, Department of Clinical and Experimental Medicine, University of Messina, AOU "G. Martino", via Consolare Valeria 1, 98124 Messina (ME), Italy.

出版信息

Int J Mol Sci. 2023 Jan 23;24(3):2259. doi: 10.3390/ijms24032259.

DOI:10.3390/ijms24032259

PMID:36768581

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9917164/

Abstract

BACKGROUND

Patients with systemic lupus erythematosus (SLE) often suffer from obstetric complications not necessarily associated with the antiphospholipid syndrome. These events may potentially result from the reduced placental synthesis of the fusogenic proteins syncytin-1 and syncytin-2, observed in women with pregnancy-related disorders. SLE patients have an aberrant noncoding (nc)RNA signature that may in turn dysregulate the expression of syncytin-1 and syncytin-2 during placentation. The aim of this research is to computationally evaluate and characterize the interaction between syncytin-1 and syncytin-2 genes and human ncRNAs and to discuss the potential implications for SLE pregnancy adverse outcomes.

METHODS

The FASTA sequences of the syncytin-1 and syncytin-2 genes were used as inputs to the Ensembl.org library to find any alignments with human ncRNA genes and their transcripts, which were characterized for their tissue expression, regulatory activity on adjacent genes, biological pathways, and potential association with human disease.

RESULTS

BLASTN analysis revealed a total of 100 hits with human long ncRNAs (lncRNAs) for the syncytin-1 and syncytin-2 genes, with median alignment scores of 151 and 66.7, respectively. Only lncRNAs TP53TG1, TTTY14, and ENSG00000273328 were reported to be expressed in placental tissue. Dysregulated expression of lncRNAs TP53TG1, LINC01239, and LINC01320 found in this analysis has previously been described in SLE patients as well as in women with a high-risk pregnancy. In addition, some of the genes adjacent to lncRNAs aligned with syncytin-1 or syncytin-2 in a regulatory region might increase the risk of pregnancy complications or SLE.

CONCLUSIONS

This is the first computational study showing alignments between syncytin-1 and syncytin-2 genes and human lncRNAs. Whether this mechanism affects syncytiotrophoblast morphogenesis in SLE females is unknown and requires further investigation.

摘要

背景

系统性红斑狼疮（SLE）患者常患有产科并发症，这些并发症不一定与抗磷脂综合征有关。这些事件可能是由于胎盘合胞蛋白 1 和 2 的合胞蛋白合成减少所致，在与妊娠相关的疾病的女性中观察到这种情况。SLE 患者存在异常的非编码（nc）RNA 特征，这可能反过来导致胎盘形成过程中合胞蛋白 1 和 2 的表达失调。本研究的目的是通过计算方法评估和描述合胞蛋白 1 和 2 基因与人类 ncRNA 之间的相互作用，并讨论其对 SLE 妊娠不良结局的潜在影响。

方法

将合胞蛋白 1 和 2 基因的 FASTA 序列作为输入，使用 Ensembl.org 库进行搜索，以找到与人类 ncRNA 基因及其转录物的任何对齐，这些转录物的特征在于其组织表达、对相邻基因的调节活性、生物途径以及与人类疾病的潜在关联。

结果

BLASTN 分析显示，合胞蛋白 1 和 2 基因与人类长 ncRNA（lncRNA）共有 100 个匹配，平均对齐分数分别为 151 和 66.7。仅报道了 lncRNA TP53TG1、TTTY14 和 ENSG00000273328 在胎盘组织中表达。在本分析中发现，lncRNA TP53TG1、LINC01239 和 LINC01320 的表达失调先前在 SLE 患者以及高危妊娠的女性中已有描述。此外，与 lncRNA 对齐的一些基因位于合胞蛋白 1 或合胞蛋白 2 的调控区域附近，可能会增加妊娠并发症或 SLE 的风险。