BACKGROUND

Apolipoprotein C-III () plays a crucial role in triglyceride metabolism and is closely associated with cardiovascular disease risk. Elevated APOC3 levels contribute to higher plasma triglycerides and increased risk of atherosclerosis, making expression an attractive and logical therapeutic target.

METHODS

While studying various transcript isoforms expressed in hepatoma cell lines (HepG2, Huh7) and healthy liver tissue using publicly available long-read RNA sequencing, we found three novel isoforms. These isoforms were validated through RT-PCR and Sanger sequencing.

RESULTS

All three novel isoforms are splicing variants of the MANE transcript, . Isoforms 1 and 2 exhibit splicing patterns similar to from exons 2-4; however, isoform 1 shares its exon 1 splicing pattern with , while isoform 2 features an extended exon 1 that includes exon 1a, the adjacent intronic region, and exon 1b. The third isoform closely resembles , but lacks exon 2, which contains the translation start codon. Remarkably, similar splicing patterns and transcript variants were observed in Caco-2 cells, a model of the small intestine, indicating that these isoforms are not liver-specific.

CONCLUSIONS

This study identifies three novel isoforms and highlights their expression in both hepatic and intestinal cell models. Further studies are needed to elucidate the functional roles of these novel isoforms and their contribution to the regulation of gene expression.