TitleLong noncoding RNAs and sulforaphane: a target for chemoprevention and suppression of prostate cancer.
Publication TypeJournal Article
Year of Publication2017
AuthorsBeaver LM, Kuintzle R, Buchanan A, Wiley MW, Glasser ST, Wong CP, Johnson GS, Chang JH, Löhr CV, Williams DE, Dashwood RH, Hendrix DA, Ho E
JournalJ Nutr Biochem
Date Published2017 04
KeywordsAnticarcinogenic Agents, Cell Line, Tumor, Gene Expression Regulation, Neoplastic, Humans, Isothiocyanates, Male, Prostatic Neoplasms, RNA, Long Noncoding, RNA, Small Interfering

Long noncoding RNAs (lncRNAs) have emerged as important in cancer development and progression. The impact of diet on lncRNA 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 lncRNAs. We analyzed whole-genome RNA-sequencing data of normal human prostate epithelial cells and prostate cancer cells treated with 15 μM SFN or dimethylsulfoxide. SFN significantly altered expression of ~100 lncRNAs in each cell type and normalized the expression of some lncRNAs that were differentially expressed in cancer cells. SFN-mediated alterations in lncRNA 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.

Alternate JournalJ. Nutr. Biochem.
PubMed ID28131897
PubMed Central IDPMC5360475
Grant ListR01 GM104977 / GM / NIGMS NIH HHS / United States
P01 CA090890 / CA / NCI NIH HHS / United States
R01 CA080176 / CA / NCI NIH HHS / United States
R01 CA122906 / CA / NCI NIH HHS / United States
R29 CA065525 / CA / NCI NIH HHS / United States
R01 CA065525 / CA / NCI NIH HHS / United States
R01 CA122959 / CA / NCI NIH HHS / United States
P30 ES000210 / ES / NIEHS NIH HHS / United States