Identification and initial functional characterization of a human vascular cell-enriched long noncoding RNA.

Area of Science:

• Molecular Biology
• Genomics
• Cardiovascular Research

Background:

• Long noncoding RNAs (lncRNAs) are increasingly recognized for their roles in gene regulation.
• Information on lncRNA expression and function in human vascular cells is limited.
• Understanding lncRNAs in vascular smooth muscle cells is crucial for cardiovascular research.

Purpose of the Study:

• Identify novel lncRNAs in human vascular smooth muscle cells.
• Investigate the function of these lncRNAs in controlling smooth muscle cell phenotypes.
• Characterize a specific vascular cell-enriched lncRNA, SENCR.

Main Methods:

• RNA sequencing (RNA-seq) of human coronary artery smooth muscle cells.
• Strand-specific reverse transcription polymerase chain reaction (PCR) and 5' rapid amplification of cDNA ends (RACE).
• RNA fluorescence in situ hybridization, biochemical fractionation, and SENCR knockdown studies.
• Scratch wound and Boyden chamber assays for migration studies.

Main Results:

• Discovered 31 unannotated lncRNAs, including SENCR, which is enriched in vascular cells.
• SENCR is a cytoplasmic lncRNA transcribed antisense to the FLI1 gene, with two splice variants.
• SENCR knockdown decreased expression of Myocardin and contractile genes, while increasing promigratory genes.
• SENCR acts as an inhibitor of smooth muscle cell migration.

Conclusions:

• SENCR is a newly identified vascular cell-enriched, cytoplasmic lncRNA.
• SENCR plays a role in maintaining the smooth muscle cell contractile phenotype.
• SENCR appears to stabilize smooth muscle cell function by regulating gene expression and inhibiting migration.