Revised Exon Structure of l-DOPA Decarboxylase (<i>DDC</i>) Reveals Novel Splice Variants Associated with Colorectal Cancer Progression

• Main Authors: Pinelopi I. Artemaki, Maria Papatsirou, Michaela A. Boti, Panagiotis G. Adamopoulos, Spyridon Christodoulou, Dido Vassilacopoulou, Andreas Scorilas, Christos K. Kontos
• Format: Article
• Language: English
• Published: MDPI AG 2020-11-01
• Series: International Journal of Molecular Sciences
• Subjects: l-aromatic amino acid decarboxylase (AADC); next-generation sequencing (NGS); transcriptomics; alternative splicing; protein isoforms; colon carcinoma
• Online Access: https://www.mdpi.com/1422-0067/21/22/8568

Colorectal cancer (CRC) is a highly heterogenous malignancy with an increased mortality rate. Aberrant splicing is a typical characteristic of CRC, and several studies support the prognostic value of particular transcripts in this malignancy. l-DOPA decarboxylase (DDC) and its derivative neurotransmitters play a multifaceted role in physiological and pathological states. Our recent data support the existence of 6 <i>DDC</i> novel exons. In this study, we investigated the existence of additional <i>DDC</i> novel exons and transcripts, and their potential value as biomarkers in CRC. Next-generation sequencing (NGS) in 55 human cell lines coupled with Sanger sequencing uncovered 3 additional <i>DDC</i> novel exons and 20 splice variants, 7 of which likely encode new protein isoforms. Eight of these transcripts were detected in CRC. An in-house qPCR assay was developed and performed in TNM II and III CRC samples for the quantification of transcripts bearing novel exons. Extensive biostatistical analysis uncovered the prognostic value of specific <i>DDC</i> novel exons for patients’ disease-free and overall survival. The revised <i>DDC</i> exon structure, the putative protein isoforms with distinct functions, and the prognostic value of novel exons highlight the pivotal role of DDC in CRC progression, indicating its potential utility as a molecular biomarker in CRC.