Vascular Anomaly Center, Department of Interventional Therapy, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
J Oral Pathol Med. 2023 Jul;52(6):554-563. doi: 10.1111/jop.13416. Epub 2023 Mar 8.
Venous malformation (VM) is a kind of congenital vascular anomaly with a high incidence of recurrence, detailed pathogenesis and standard treatment of VM still lack now. Increasing evidence showed exosomal RNA plays a pivotal role in various diseases. However, the underlying mechanism of VM based on the potential differentially exosomal RNAs remains unclear.
Comparative high-throughput sequencing with serum exosomes from three VM patients and three healthy donors was used to explore differentially expressed (DE) circRNAs, DE lncRNAs, and DE mRNAs involving the formation of VM. We identified and verified DE circRNAs, DE lncRNAs, and DE mRNAs via qRT-PCR assay. We explored the potential functions of these exosomal DE non-coding RNAs via performing further Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis. Besides, circRNA/lncRNA-miRNA-mRNA linkages were also constructed to find their potential relationships in VM.
A total of 121 circRNAs, 53 lncRNAs, and 42 mRNAs (|log FC| ≥ 2.0, FDR <0.05, n = 3) were determined to be differentially expressed. QRT-PCR validated that these top-changed DE circRNAs, lncRNAs, and mRNAs had significant expression changes. Functional studies demonstrated that DE circRNAs play a pivotal role in thyroid hormone signaling pathway, DE lncRNAs function as a key regulator in MAPK signaling pathway and DE miRNAs participate in the process of hepatocellular carcinoma mostly.
Our study comprehensively depicted exosomal DE non-coding RNAs networks related to the pathogenesis of VM which can provide new insight into, a novel target for treating VM.
静脉畸形（VM）是一种先天性血管畸形，其复发率较高，目前对 VM 的详细发病机制和标准治疗方法仍缺乏了解。越来越多的证据表明外泌体 RNA 在各种疾病中发挥着关键作用。然而，基于潜在差异表达的外泌体 RNA 的 VM 发病机制尚不清楚。
采用比较高通量测序方法，对 3 例 VM 患者和 3 例健康供体的血清外泌体进行研究，以探讨涉及 VM 形成的差异表达 circRNA、lncRNA 和 mRNA。通过 qRT-PCR 检测鉴定和验证差异表达的 circRNA、lncRNA 和 mRNA。通过进一步进行基因本体论和京都基因与基因组百科全书富集分析，探索这些外泌体差异表达非编码 RNA 的潜在功能。此外，还构建了 circRNA/lncRNA-miRNA-mRNA 联系，以发现它们在 VM 中的潜在关系。
共确定了 121 个 circRNA、53 个 lncRNA 和 42 个 mRNA（|logFC|≥2.0，FDR<0.05，n=3）存在差异表达。qRT-PCR 验证了这些 top 差异表达的 DE circRNA、lncRNA 和 mRNA 具有显著的表达变化。功能研究表明，DE circRNAs 在甲状腺激素信号通路中发挥关键作用，DE lncRNAs 在 MAPK 信号通路中作为关键调节剂发挥作用，DE miRNAs 主要参与肝细胞癌的发生过程。
本研究全面描绘了与 VM 发病机制相关的外泌体差异表达非编码 RNA 网络，为治疗 VM 提供了新的靶点。
