Novel transcriptional and DNA methylation abnormalities of SORT1 Gene in non-small cell lung cancer

Journal article

Acha-Sagredo, Amelia, Wilson, C., Garcia Bediaga, Naiara, Kalirai, Helen, Davies, M., Coupland, S., Field, John K and Liloglou, T. 2024. Novel transcriptional and DNA methylation abnormalities of SORT1 Gene in non-small cell lung cancer. Cancers. 16 (11), p. 2154. https://doi.org/10.3390/cancers16112154
AuthorsAcha-Sagredo, Amelia, Wilson, C., Garcia Bediaga, Naiara, Kalirai, Helen, Davies, M., Coupland, S., Field, John K and Liloglou, T.
AbstractSortilin is an important regulator with potential tumour-suppressor function by limiting EGFR signalling. In this study, we undertook a comprehensive expression analysis of sortilin transcript variants and the DNA methylation status of their corresponding promoters in human non-small cell carcinomas (NSCLCs). RNA/DNA was extracted from 81 NSCLC samples and paired normal tissue. mRNA expression was measured by qPCR and DNA methylation determined by pyrosequencing. BigDye-terminator sequencing was used to confirm exon-8 alternative splicing. Results demonstrated that both SORT1A and SORT1B variants were downregulated in lung tumours. The SORT1A/SORT1B expression ratio was higher in tumours compared to normal tissue. SORT1B promoter hypermethylation was detected in lung tumours compared to normal lung (median difference 14%, Mann-Whitney test = 10 ). Interestingly, SORT1B is hypermethylated in white blood cells, but a small and very consistent drop in methylation (6%, = 10 ) was observed in the lung cancer cases compared to control subjects. We demonstrate that the SORT1B exon-8 splice variation, reported in sequence databases, is also a feature of SORT1A. The significantly altered quantitative and qualitative characteristics of sortilin mRNA in NSCLC indicate a significant involvement in tumour pathogenesis and may have significant impact for its utility as a predictive marker in lung cancer management.
Keywordssortilin; non-small cell lung cancer; splicing; DNA methylation
Year2024
JournalCancers
Journal citation16 (11), p. 2154
PublisherMDPI AG
ISSN2072-6694
Digital Object Identifier (DOI)https://doi.org/10.3390/cancers16112154
https://doi.org/cancers16112154
Official URLhttps://www.mdpi.com/2072-6694/16/11/2154
FunderRoy Castle Lung Cancer Foundation
North West Cancer Research
Publication dates
Print01 Jun 2024
Online06 Jun 2024
Publication process dates
Deposited12 Jun 2024
Accepted03 Jun 2024
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Open
Output statusPublished
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