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LncRNA MEG3 aggravates acute pulmonary embolism-induced pulmonary arterial hypertension by regulating

Jianfeng Song1, Jinyan Shao1, Shuili Yu1

  • 1Emergency Department, Minhang Hospital, Fudan University, 170 Xinsong Road, Minhang District, Shanghai 201199, PR China.

International Journal of Biological Macromolecules
|November 17, 2024
PubMed

Insights

Long non-coding RNA MEG3 aggravates acute pulmonary embolism-induced pulmonary hypertension by regulating the miR-34a-3p/DUSP1 pathway. This finding offers a potential new biomarker for pulmonary hypertension treatment.

Area of Science:

  • Cardiovascular Research
  • Molecular Biology
  • Pulmonary Medicine

Background:

  • Acute pulmonary embolism (APE)-induced pulmonary artery hypertension (PAH) is a critical condition.
  • The miR-34a-3p/DUSP1 pathway plays a role in regulating pulmonary arterial wall thickening and smooth muscle cell proliferation.

Purpose of the Study:

  • To investigate the role of long non-coding RNAs (lncRNAs) in regulating the miR-34a-3p/DUSP1 axis in APE and PAH.
  • To explore MEG3 as a potential regulator in this pathway.

Main Methods:

  • In vitro studies using platelet-derived growth factor-BB (PDGF-BB)-induced human pulmonary arterial smooth muscle cells (hPASMCs).
  • In vivo studies using a rat model of APE.
  • Manipulation of MEG3 and miR-34a-3p levels using overexpression and knockdown techniques.
  • Assessment of cell viability, proliferation, and mean pulmonary arterial pressure (mPAP).

Main Results:

  • MEG3 was found to target miR-34a-3p.
  • MEG3 overexpression exacerbated PDGF-BB-induced hPASMC proliferation and increased mPAP in APE rats.
  • MEG3 influenced the expression of key genes including NOR-1, PCNA, and DUSP1, while downregulating miR-34a-3p.
  • Inhibition of MEG3 (shMEG3) produced opposite effects.
  • MiR-34a-3p mimic reversed MEG3 overexpression effects, and DUSP1 overexpression counteracted MEG3 downregulation effects.

Conclusions:

  • MEG3 aggravates APE-induced PAH by modulating the miR-34a-3p/DUSP1 axis.
  • MEG3 presents potential as a novel biomarker for PAH treatment.
Keywords:
Acute pulmonary embolismDUSP1MEG3Pulmonary arterial hypertensionhPASMCsmiR-34a-3p

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