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
Authors | Acha-Sagredo, Amelia, Wilson, C., Garcia Bediaga, Naiara, Kalirai, Helen, Davies, M., Coupland, S., Field, John K and Liloglou, T. |
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Abstract | Sortilin 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. |
Keywords | sortilin; non-small cell lung cancer; splicing; DNA methylation |
Year | 2024 |
Journal | Cancers |
Journal citation | 16 (11), p. 2154 |
Publisher | MDPI AG |
ISSN | 2072-6694 |
Digital Object Identifier (DOI) | https://doi.org/10.3390/cancers16112154 |
https://doi.org/cancers16112154 | |
Official URL | https://www.mdpi.com/2072-6694/16/11/2154 |
Funder | Roy Castle Lung Cancer Foundation |
North West Cancer Research | |
Publication dates | |
01 Jun 2024 | |
Online | 06 Jun 2024 |
Publication process dates | |
Deposited | 12 Jun 2024 |
Accepted | 03 Jun 2024 |
Publisher's version | File Access Level Open |
Supplemental file | File Access Level Open |
Output status | Published |
Additional information | Publications router: Date 2024-06-03 of type 'accepted_date' included in notification. |
License | CC BY |
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https://repository.canterbury.ac.uk/item/98178/novel-transcriptional-and-dna-methylation-abnormalities-of-sort1-gene-in-non-small-cell-lung-cancer
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