Modulation of Long Noncoding RNAs by Risk SNPs Underlying Genetic Predispositions to Prostate Cancer

Overview

Journal Nat Genet

Specialty Genetics

Date 2016 Aug 16

PMID 27526323

Citations 132

Authors

Haiyang Guo

Musaddeque Ahmed

Fan Zhang

Cindy Q Yao

Side Li

Yi Liang

Junjie Hua

Fraser Soares

Yifei Sun

Jens Langstein

Yuchen Li

Christine Poon

Swneke D Bailey

Kinjal Desai

Teng Fei

Qiyuan Li

Dorota H Sendorek

Michael Fraser

John R Prensner

Trevor J Pugh

Mark Pomerantz

Robert G Bristow

Mathieu Lupien

Felix Y Feng

Paul C Boutros

Matthew L Freedman

Martin J Walsh

Housheng Hansen He

Affiliations

Soon will be listed here.

Abstract

Long noncoding RNAs (lncRNAs) represent an attractive class of candidates to mediate cancer risk. Through integrative analysis of the lncRNA transcriptome with genomic data and SNP data from prostate cancer genome-wide association studies (GWAS), we identified 45 candidate lncRNAs associated with risk to prostate cancer. We further evaluated the mechanism underlying the top hit, PCAT1, and found that a risk-associated variant at rs7463708 increases binding of ONECUT2, a novel androgen receptor (AR)-interacting transcription factor, at a distal enhancer that loops to the PCAT1 promoter, resulting in upregulation of PCAT1 upon prolonged androgen treatment. In addition, PCAT1 interacts with AR and LSD1 and is required for their recruitment to the enhancers of GNMT and DHCR24, two androgen late-response genes implicated in prostate cancer development and progression. PCAT1 promotes prostate cancer cell proliferation and tumor growth in vitro and in vivo. These findings suggest that modulating lncRNA expression is an important mechanism for risk-associated SNPs in promoting prostate transformation.

Citing Articles

Androgen receptor dynamics in prostate cancer: from disease progression to treatment resistance.

Li C, Cheng D, Li P Front Oncol. 2025; 15:1542811.

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Challenges in LncRNA Biology: Views and Opinions.

Adjeroh D, Zhou X, Paschoal A, Dimitrova N, Derevyanchuk E, Shkurat T Noncoding RNA. 2024; 10(4).

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DHCR24 in Tumor Diagnosis and Treatment: A Comprehensive Review.

Fu X, Wang Z Technol Cancer Res Treat. 2024; 23:15330338241259780.

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