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

International Journal of Molecular Sciences
Pinelopi I ArtemakiChristos K Kontos

Abstract

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 DDC novel exons. In this study, we investigated the existence of additional DDC 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 DDC 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 DDC novel exons for patients' disease-free and overall survival. The revised DDC exon structure, the putative protein isoforms with distinct functions, and the prognostic value of novel exons highlight the pivo...Continue Reading

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Citations

Mar 7, 2021·International Journal of Molecular Sciences·Pinelopi I Artemaki, Christos K Kontos

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Datasets Mentioned

BETA
MN447448.1
KP729825.2
KP729826.2
MW092772.1

Methods Mentioned

BETA
biopsy
PCR
PCRs
Electrophoresis
glycosylation

Software Mentioned

TASSER
Alternative Splicing Detection Tool ( ASDT )
Torrent [UNK]
NetNGlyc
NetOGlyc
tile
NetPhos
Primer BLAST
ExPASy

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