Discovery of Novel APOC3 Isoforms in Hepatic and Intestinal Cell Models Using Long-Read RNA Sequencing

Kara Farstad-O’Halloran; Anuradha Sooda; Tooba Iqbal; Steve Wilton; May T. Aung-Htut

doi:10.3390/genes16040412

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Discovery of Novel APOC3 Isoforms in Hepatic and Intestinal Cell Models Using Long-Read RNA Sequencing

Journal article

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Peer reviewed

Discovery of Novel APOC3 Isoforms in Hepatic and Intestinal Cell Models Using Long-Read RNA Sequencing

Kara Farstad-O’Halloran, Anuradha Sooda, Tooba Iqbal, Steve Wilton and May T. Aung-Htut

Genes, Vol.16(4), 412

2025

DOI: https://doi.org/10.3390/genes16040412

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Abstract

apolipoprotein C-III (APOC3)

triglyceride metabolism

cardiovascular disease

novel transcript isoforms

long-read RNA sequencing

Background Apolipoprotein C-III (APOC3) 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 APOC3 expression an attractive and logical therapeutic target. Methods While studying various APOC3 transcript isoforms expressed in hepatoma cell lines (HepG2, Huh7) and healthy liver tissue using publicly available long-read RNA sequencing, we found three novel APOC3 isoforms. These isoforms were validated through RT-PCR and Sanger sequencing. Results All three novel isoforms are splicing variants of the MANE transcript, APOC3-201. Isoforms 1 and 2 exhibit splicing patterns similar to APOC3-201 from exons 2–4; however, isoform 1 shares its exon 1 splicing pattern with APOC3-203, while isoform 2 features an extended exon 1 that includes exon 1a, the adjacent intronic region, and exon 1b. The third isoform closely resembles APOC3-201, but lacks exon 2, which contains the translation start codon. Remarkably, similar APOC3 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 APOC3 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 APOC3 gene expression.

Details

Title: Discovery of Novel APOC3 Isoforms in Hepatic and Intestinal Cell Models Using Long-Read RNA Sequencing
Authors/Creators: Kara Farstad-O’Halloran - Murdoch University
Anuradha Sooda - Avenir Health
Tooba Iqbal - Murdoch University
Steve Wilton - Murdoch University
May T. Aung-Htut - Murdoch University
Publication Details: Genes, Vol.16(4), 412
Publisher: MDPI; BASEL
Number of pages: 12
Identifiers: 991005760133807891
Murdoch Affiliation: Personalised Medicine Centre; Centre for Molecular Medicine and Innovative Therapeutics
Language: English
Resource Type: Journal article

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Collaboration types: Domestic collaboration
Citation topics: 1 Clinical & Life Sciences; 1.68 Lipids; 1.68.69 Lipoprotein Metabolism
Web Of Science research areas: Genetics & Heredity
ESI research areas: Molecular Biology & Genetics