Scholarlink

<p>The regulatory mechanism of the long noncoding RNA SNHG6 in acute pulmonary embolism (APE) remains unclear. This study aimed to investigate the potential molecular mechanisms of SNHG6 in APE. This study established a clinical cohort comprising 120 APE patients and 120 healthy controls. It combined in vitro experiments using human pulmonary arterial smooth muscle cells (PASMCs) with in vivo experiments employing an autologous blood clot model of APE in Sprague-Dawley (SD) rats, measuring mean pulmonary artery pressure (mPAP). RT-qPCR was used to detect target gene expression. The CCK-8 assay evaluated cell proliferation, while the ELISA and western blot assays measured the relevant protein levels. The RIP assay and dual luciferase assay validated the target binding relationship. SNHG6 was significantly overexpressed in both serum samples from APE patients and lung tissues from model rats. In this exploratory case-control cohort, serum SNHG6 exhibited significant discriminatory capacity between APE patients and healthy controls (AUC = 0.9145) and showed an independent cross‑sectional association with APE status in multivariate analysis within this selected cohort. However, because serum SNHG6 was measured after diagnosis, this association should be interpreted strictly as a correlative finding rather than as evidence of prospective predictive or etiologic value. These findings require validation in clinically relevant populations with differential diagnoses. Mechanistic studies revealed that SNHG6 targeted and regulated miR-429, which in turn targeted DUSP1. In cultured PASMCs, SNHG6 acted as a competitive endogenous RNA to sequester miR-429, thereby releasing its suppression on the downstream target gene DUSP1. This upregulated the expression of proliferation-related molecules such as NOR-1 and PCNA, positively regulating PDGF-BB-induced PASMC cell proliferation. Animal experiments performed at a 7‑day subacute endpoint demonstrated that SNHG6 perturbation was associated with altered mean pulmonary artery pressure and early proliferative molecular markers during the early phase following embolic challenge. In cultured PASMCs, specific sponging of miR-429 by SNHG6 may attenuate the inhibitory effect of miR-429 on DUSP1, potentially contributing to exacerbated APE pathological manifestations.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Long non-coding RNA SNHG6 promotes the proliferation of PASMCs cells through the miR-429/DUSP1 axis during early/subacute vascular responses to pulmonary embolism

  • 期刊论文

  • 发表日期：

    2026年8月4日

查看全文
  • Long Zeng,
  • Shu Wang,
  • Qian Wu,
  • Wenfei Xu,
  • Yue Wu,
  • Min Ou

摘要

The regulatory mechanism of the long noncoding RNA SNHG6 in acute pulmonary embolism (APE) remains unclear. This study aimed to investigate the potential molecular mechanisms of SNHG6 in APE. This study established a clinical cohort comprising 120 APE patients and 120 healthy controls. It combined in vitro experiments using human pulmonary arterial smooth muscle cells (PASMCs) with in vivo experiments employing an autologous blood clot model of APE in Sprague-Dawley (SD) rats, measuring mean pulmonary artery pressure (mPAP). RT-qPCR was used to detect target gene expression. The CCK-8 assay evaluated cell proliferation, while the ELISA and western blot assays measured the relevant protein levels. The RIP assay and dual luciferase assay validated the target binding relationship. SNHG6 was significantly overexpressed in both serum samples from APE patients and lung tissues from model rats. In this exploratory case-control cohort, serum SNHG6 exhibited significant discriminatory capacity between APE patients and healthy controls (AUC = 0.9145) and showed an independent cross‑sectional association with APE status in multivariate analysis within this selected cohort. However, because serum SNHG6 was measured after diagnosis, this association should be interpreted strictly as a correlative finding rather than as evidence of prospective predictive or etiologic value. These findings require validation in clinically relevant populations with differential diagnoses. Mechanistic studies revealed that SNHG6 targeted and regulated miR-429, which in turn targeted DUSP1. In cultured PASMCs, SNHG6 acted as a competitive endogenous RNA to sequester miR-429, thereby releasing its suppression on the downstream target gene DUSP1. This upregulated the expression of proliferation-related molecules such as NOR-1 and PCNA, positively regulating PDGF-BB-induced PASMC cell proliferation. Animal experiments performed at a 7‑day subacute endpoint demonstrated that SNHG6 perturbation was associated with altered mean pulmonary artery pressure and early proliferative molecular markers during the early phase following embolic challenge. In cultured PASMCs, specific sponging of miR-429 by SNHG6 may attenuate the inhibitory effect of miR-429 on DUSP1, potentially contributing to exacerbated APE pathological manifestations.