Long noncoding RNAs and sulforaphane: a target for chemoprevention and suppression of prostate cancer

卷:42

Beaver, Laura M. ; Kuintzle, Rachael ; Buchanan, Alex ; Wiley, Michelle W. ; Glasser, Sarah T. ; Wong, Carmen P. ; Johnson, Gavin S. ; Chang, Jeff H. ; Lohr, Christiane V. ; Williams, David E. ; Dashwood, Roderick H. ; Hendrix, David A. ; Ho, Emily

Oregon State Univ

关键词: Chemoprevention;    Long noncoding RNA;    LINC01116;    Prostate cancer;    Sulforaphane;    Diet-gene interactions;   

DOI  :  10.1016/j.jnutbio.2017.01.001

学科分类：食品科学和技术

【 摘 要 】

Long noncoding RNAs (lncRNAs) have emerged as important in cancer development and progression. The impact of diet on IncRNA expression is largely unknown. Sulforaphane (SFN), obtained from vegetables like broccoli, can prevent and suppress cancer formation. Here we tested the hypothesis that SFN attenuates the expression of cancer-associated IncRNAs. We analyzed whole-genome RNA-sequencing data of normal human prostate epithelial cells and prostate cancer cells treated with 15 M SFN or dimethylsulfoxide. SFN significantly altered expression of similar to 100 lncRNAs in each cell type and normalized the expression of some lncRNAs that were differentially expressed in cancer cells. SFN-mediated alterations in IncRNA expression correlated with genes that regulate cell cycle, signal transduction and metabolism. LINC01116 was functionally investigated because it was overexpressed in several cancers, and was transcriptionally repressed after SFN treatment. Knockdown of LINC01116 with siRNA decreased proliferation of prostate cancer cells and significantly up-regulated several genes including GAPDH (regulates glycolysis), MAP1LC3B2 (autophagy) and H2AFY (chromatin structure). A four-fold decrease in the ability of the cancer cells to form colonies was found when the LINC01116 gene was disrupted through a CRISPR/CAS9 method, further supporting an oncogenic function for LINC01116 in PC-3 cells. We identified a novel isoform of LINC01116 and bioinformatically investigated the possibility that LINC01116 could interact with target genes via ssRNA:dsDNA triplexes. Our data reveal that chemicals from the diet can influence the expression of functionally important lncRNAs, and suggest a novel mechanism by which SFN may prevent and suppress prostate cancer. Published by Elsevier Inc.