Long noncoding RNA LISPR1 is required for S1P signaling and endothelial cell function

Area of Science:

• Molecular Biology
• Cell Biology
• Genomics

Background:

• Sphingosine-1-Phosphate (S1P) signaling is crucial in endothelial cells, primarily mediated by S1P receptor 1 (S1PR1).
• Long noncoding RNAs (lncRNAs) are emerging regulators of gene expression.
• LISPR1, a lncRNA antisense to S1PR1, is investigated for its role in endothelial S1P signaling.

Purpose of the Study:

• To determine if LISPR1 regulates endothelial S1PR1 expression and subsequent S1P signaling.
• To elucidate the mechanism by which LISPR1 influences S1PR1 expression.
• To assess the relevance of LISPR1 and S1PR1 in human pulmonary diseases.

Main Methods:

• In vitro transcription/translation and coding potential assessment to confirm LISPR1 as noncoding.
• qRT-PCR and RNA-Seq to analyze LISPR1 and S1PR1 expression in endothelial cells and lung tissue.
• LISPR1 knockdown experiments to evaluate effects on endothelial cell function and S1PR1 regulation.

Main Results:

• LISPR1 is a noncoding RNA, localized in cytoplasm and nucleus, highly expressed in endothelial cells and lung tissue.
• LISPR1 and S1PR1 expression are downregulated in COPD and induced by inflammation, shear stress, and statins.
• LISPR1 knockdown reduced S1PR1 expression, impaired S1P-induced endothelial cell migration and spheroid outgrowth, and altered transcriptional regulation of S1PR1.

Conclusions:

• The lncRNA LISPR1 is a novel regulator of endothelial S1PR1 expression and function.
• LISPR1 plays a critical role in S1P downstream signaling pathways in endothelial cells.
• LISPR1 represents a potential therapeutic target for pulmonary diseases characterized by altered S1P signaling.