ANRIL overexpression globally induces expression and alternative splicing of genes involved in inflammation in HUVECs

Long non-coding (lnc)RNAs serve important cellular functions and certain lncRNAs have roles in different mechanisms of gene regulation. lncRNA-antisense non-coding RNA in the INK4 locus (ANRIL) affects cell inflammation; however, the potential genes underlying the inflammatory response regulated by ANRIL remain unclear. In the present study, the potential function of ANRIL in regulating gene expression and alternative splicing was assessed. ANRIL-regulated human umbilical vein endothelial cell (HUVEC) transcriptome was obtained using high-throughput RNA sequencing (RNA-seq) to evaluate the potential role of ANRIL. Following plasmid transfection, gene expression profile and alternative splicing pattern of HUVECs overexpressing ANRIL were analyzed using RNA-seq. ANRIL overexpression affected the transcription levels of genes associated with the inflammatory response, NF-kappa B signaling pathway, type I interferon-mediated signal transduction pathway and innate immune response. ANRIL regulated the alternative splicing of hundreds of genes with functions such as gene expression, translation, DNA repair, RNA processing and participation in the NF-kappa B signaling pathway. Many of these genes serve a key role in the inflammatory response. ANRIL-regulated inflammatory response may be achieved by regulating alternate splicing and transcription. The present study broadened the understanding of ANRIL-mediated gene regulation mechanisms and clarified the role of ANRIL in mediating inflammatory response mechanisms.

Automated summary

This study assessed the potential function of antisense non-coding RNA in the INK4 locus (ANRIL) in gene expression and alternative splicing. The results showed that ANRIL overexpression affects the transcription levels of genes associated with the inflammatory response, NF-kappa B signaling pathway, type I interferon-mediated signal transduction pathway, and innate immune response. ANRIL also regulates the alternative splicing of hundreds of genes, many of which play key roles in the inflammatory response. By regulating alternative splicing and transcription, ANRIL is involved in regulating the inflammatory response mechanisms.