Colorectal cancer-associated SNP rs17042479 is involved in the regulation of NAF1 promoter activity
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Colorectal cancer-associated SNP rs17042479 is involved in the regulation of NAF1 promoter activity. / Olsson, Josephine B.; Gugerel, Marietta B.; Jessen, Stine B.; Jørgensen, Jannie; Gögenur, Ismail; Hansen, Camilla; Kirkeby, Lene T.; Olsen, Jørgen; Pedersen, Ole B.V.; Vestlev, Peter M.; Dahlgaard, Katja; Troelsen, Jesper T.
I: PLoS ONE, Bind 17, Nr. 9 , e0274033, 2022.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Colorectal cancer-associated SNP rs17042479 is involved in the regulation of NAF1 promoter activity
AU - Olsson, Josephine B.
AU - Gugerel, Marietta B.
AU - Jessen, Stine B.
AU - Jørgensen, Jannie
AU - Gögenur, Ismail
AU - Hansen, Camilla
AU - Kirkeby, Lene T.
AU - Olsen, Jørgen
AU - Pedersen, Ole B.V.
AU - Vestlev, Peter M.
AU - Dahlgaard, Katja
AU - Troelsen, Jesper T.
N1 - Publisher Copyright: © 2022 Olsson et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2022
Y1 - 2022
N2 - A novel risk locus at 4q32.2, located between the Nuclear Assembly Factor 1 (NAF1) and Follistatin Like 5 (FSTL5) genes, was associated with increased risk of developing colorectal cancer (CRC), with SNP rs17042479 being the most associated. However, the link between CRC development and the risk locus at 4q32.2 is unknown. We investigated the promoter activity of NAF1 and FSTL5 and analyzed the risk locus at 4q32.2 as gene regulatory region. Our results showed that the activity of the FSTL5 promoter was low compared to the NAF1 promoter. Analyses of the NAF1 promoter in conjunction with the region containing the risk locus at 4q32.2 showed that the region functions as gene regulatory region with repressor activity on NAF1 promoter activity. The SNP rs17042479(G) increased the repressor effect of the region. CRC patients’ biopsies were genotyped for SNP rs17042479(A/G), and NAF1 expression profiles were examined. We found an association between SNP rs17042479 (G), cancer stage and tumor location. Additionally, patients with SNP rs17042479(G) showed lower NAF1 expression in comparison to patients with SNP rs17042479(A) in tumor tissue and the NAF1 expression in tumor tissue was lower compared to healthy tissue. The results in the study imply that reduced NAF1 expression in the tumor contribute to a more aggressive phenotype. Furthermore, this study suggests that the SNP rs17042479(G) change the expression of NAF1 and thereby increases the risk of developing CRC.
AB - A novel risk locus at 4q32.2, located between the Nuclear Assembly Factor 1 (NAF1) and Follistatin Like 5 (FSTL5) genes, was associated with increased risk of developing colorectal cancer (CRC), with SNP rs17042479 being the most associated. However, the link between CRC development and the risk locus at 4q32.2 is unknown. We investigated the promoter activity of NAF1 and FSTL5 and analyzed the risk locus at 4q32.2 as gene regulatory region. Our results showed that the activity of the FSTL5 promoter was low compared to the NAF1 promoter. Analyses of the NAF1 promoter in conjunction with the region containing the risk locus at 4q32.2 showed that the region functions as gene regulatory region with repressor activity on NAF1 promoter activity. The SNP rs17042479(G) increased the repressor effect of the region. CRC patients’ biopsies were genotyped for SNP rs17042479(A/G), and NAF1 expression profiles were examined. We found an association between SNP rs17042479 (G), cancer stage and tumor location. Additionally, patients with SNP rs17042479(G) showed lower NAF1 expression in comparison to patients with SNP rs17042479(A) in tumor tissue and the NAF1 expression in tumor tissue was lower compared to healthy tissue. The results in the study imply that reduced NAF1 expression in the tumor contribute to a more aggressive phenotype. Furthermore, this study suggests that the SNP rs17042479(G) change the expression of NAF1 and thereby increases the risk of developing CRC.
U2 - 10.1371/journal.pone.0274033
DO - 10.1371/journal.pone.0274033
M3 - Journal article
C2 - 36067202
AN - SCOPUS:85137745666
VL - 17
JO - PLoS ONE
JF - PLoS ONE
SN - 1932-6203
IS - 9
M1 - e0274033
ER -
ID: 327138476