Prostate cancer risk SNP rs10993994 is a trans-eQTL for SNHG11 mediated through MSMB Journal Article
| Authors: | Bicak, M.; Wang, X.; Gao, X.; Xu, X.; Väänänen, R. M.; Taimen, P.; Lilja, H.; Pettersson, K.; Klein, R. J. |
| Article Title: | Prostate cancer risk SNP rs10993994 is a trans-eQTL for SNHG11 mediated through MSMB |
| Abstract: | How genome-wide association studies-identified single-nucleotide polymorphisms (SNPs) affect remote genes remains unknown. Expression quantitative trait locus (eQTL) association meta-analysis on 496 prostate tumor and 602 normal prostate samples with 117 SNPs revealed novel cis-eQTLs and trans-eQTLs. Mediation testing and colocalization analysis demonstrate that MSMB is a cis-acting mediator for SNHG11 (P < 0.01). Removing rs10993994 in LNCaP cell lines by CRISPR/Cas9 editing shows that the C-allele corresponds with an over 100-fold increase in MSMB expression and 5-fold increase in SNHG11 compared with the T-allele. Colocalization analysis confirmed that the same set of SNPs associated with MSMB expression is associated with SNHG11 expression (posterior probability of shared variants is 66.6% in tumor and 91.4% in benign). These analyses further demonstrate variants driving MSMB expression differ in tumor and normal, suggesting regulatory network rewiring during tumorigenesis. © The Author(s) 2020. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com. |
| Journal Title: | Human Molecular Genetics |
| Volume: | 29 |
| Issue: | 10 |
| ISSN: | 0964-6906 |
| Publisher: | Oxford University Press |
| Date Published: | 2020-05-15 |
| Start Page: | 1581 |
| End Page: | 1591 |
| Language: | English |
| DOI: | 10.1093/hmg/ddaa026 |
| PUBMED: | 32065238 |
| PROVIDER: | scopus |
| PMCID: | PMC7526792 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 3 August 2020 -- Source: Scopus |
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