LncRNA H19 promotes vascular remodeling by inhibiting MFN2

IF 4 4区生物学 Q1 GENETICS & HEREDITY

Functional & Integrative Genomics Pub Date : 2026-09-14 DOI:10.1007/s10142-026-02043-3

Shu-Yan Yang, Li Meng, Si-Fan Wang, Ying-Qing Xie, Li-Yun Yang, Sen Wang, Zhao-Yi Wang, Xu-Zhe Li, Yi-Ming Li, Ya-Xing Xu, Xin Xu, Yang Li

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引用次数: 0

Abstract

Neointimal hyperplasia, featuring excessive proliferation and migration of vascular smooth muscle cells (VSMCs), is crucial in vascular remodeling diseases. Long non-coding RNA (lncRNA) H19 promotes vascular remodeling, yet underlying mechanisms remain incompletely elucidated. Here, we investigated whether H19 acts via its derivative miR-675-5p. Bioinformatics found a conserved H19/miR-675-5p/MFN2 (mitofusin 2) axis. Cell assays were performed to evaluate the effects of H19 and miR-675-5p on VSMC proliferation and migration. The dual-luciferase reporter gene assay was used to assess the interaction between miR-675-5p and Mfn2 mRNA. The mouse model of common carotid artery ligation was used to evaluate the role of H19 in neointimal hyperplasia. Our data suggested that knockdown of H19 inhibited VSMC proliferation and migration, as well as neointimal hyperplasia. Mechanistically, H19 regulated MFN2 through miR-675-5p, leading to ERK1/2 (extracellular signal-regulated kinase 1/2) activation. In conclusion, we suggest that targeting the H19/miR-675-5p/MFN2/ERK1/2 axis may help to treat vascular remodeling diseases.

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LncRNA H19通过抑制MFN2促进血管重塑。

血管平滑肌细胞（VSMCs）的过度增殖和迁移是血管重塑疾病的关键。长链非编码RNA (lncRNA) H19促进血管重构，但其潜在机制尚未完全阐明。在这里，我们研究了H19是否通过其衍生物miR-675-5p起作用。生物信息学发现保守的H19/miR-675-5p/MFN2 （mitofusin 2）轴。通过细胞检测来评估H19和miR-675-5p对VSMC增殖和迁移的影响。双荧光素酶报告基因检测用于评估miR-675-5p与Mfn2 mRNA之间的相互作用。采用小鼠颈总动脉结扎模型评价H19在新生内膜增生中的作用。我们的数据表明，敲低H19抑制VSMC的增殖和迁移，以及新生内膜增生。在机制上，H19通过miR-675-5p调节MFN2，导致ERK1/2（细胞外信号调节激酶1/2）激活。综上所述，我们认为靶向H19/miR-675-5p/MFN2/ERK1/2轴可能有助于治疗血管重塑疾病。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Functional & Integrative Genomics 生物-遗传学

CiteScore

3.50

自引率

3.40%

发文量

审稿时长

2 months

期刊介绍： Functional & Integrative Genomics is devoted to large-scale studies of genomes and their functions, including systems analyses of biological processes. The journal will provide the research community an integrated platform where researchers can share, review and discuss their findings on important biological questions that will ultimately enable us to answer the fundamental question: How do genomes work?