LIPE-AS1: Putative Regulator of CEACAM1 Biology

In humans, Carcinoembryonic Antigen-Related Cell Adhesion Molecule 1 (CEACAM1) undergoes extensive alternative splicing to generate either a short (S) cytoplasmic tail involved in binding to actin, tropomyosin, calmodulin, and is involved in normal mammary lumen formation development. The long form (L) has two cytosolic phosphotyrosine residues and immunoreceptor tyrosine-based inhibitory motifs signaling motifs, predominant in immune cells that bind SHP-1 when phosphorylated and convey inhibitory activities to CEACAM1. Long non-coding RNAs (lncRNAs) have emerged as critical regulators of gene expression in diverse biological processes. In this study, we investigated whether the noncoding RNA, LIPE-AS1, is involved in putative key regulatory gene regulation of CEACAM1. The genomic organization of sense strand LIPE-AS1 on chromosome 19 overlaps four genes in anti-sense orientation (LIPE, CXCL17, CEACAM1, CEACAM8). We identified myeloid zinc finger-1 (MZF-1) as a transcription factor that can activate LIPE-AS1 mRNA within +250 bp from the transcriptional start site (TSS) in HeLa cells. Interestingly, over-expression of MZF-1 not only increases LIPE-AS1 mRNA as expected but CEACAM1 mRNA as well despite the fact that these cervical carcinoma cells do not endogenously express CEACAM1 protein. When the alternative splicing mechanism was investigated, we detected a preference for the long isoform of CEACAM1 suggesting a possible role in inflammation immune regulation. The novel activities attributed to LIPE-AS1 indicate a mechanism for gene regulation at the transcriptional level.