title: Long noncoding RNAs and sulforaphane: a target for chemoprevention and suppression of prostate cancer.
abstract: 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.
authors.affiliation: Biological and Population Health Sciences, Oregon State University, 103 Milam Hall, Corvallis, OR 97331; Linus Pauling Institute, Oregon State University, 307 Linus Pauling Science Center, Corvallis, OR 97331. Electronic address: Laura.Beaver@oregonstate.edu.
authors.forename: Laura M
authors.initials: LM
authors.lastname: Beaver
authors.affiliation: Department of Biochemistry and Biophysics, Oregon State University, 2011 Agriculture and Life Sciences Building, Corvallis, OR 97331. Electronic address: kuintzlr@oregonstate.edu.
authors.forename: Rachael
authors.initials: R
authors.lastname: Kuintzle
authors.affiliation: Biological and Population Health Sciences, Oregon State University, 103 Milam Hall, Corvallis, OR 97331; Department of Botany and Plant Pathology, Oregon State University, 2082 Cordley Hall, Corvallis, OR 97331. Electronic address: buchanae@gmail.com.
authors.forename: Alex
authors.initials: A
authors.lastname: Buchanan
authors.affiliation: Department of Biochemistry and Biophysics, Oregon State University, 2011 Agriculture and Life Sciences Building, Corvallis, OR 97331. Electronic address: wileym@oregonstate.edu.
authors.forename: Michelle W
authors.initials: MW
authors.lastname: Wiley
authors.affiliation: Biological and Population Health Sciences, Oregon State University, 103 Milam Hall, Corvallis, OR 97331. Electronic address: glasser.sarah@gmail.com.
authors.forename: Sarah T
authors.initials: ST
authors.lastname: Glasser
authors.affiliation: Biological and Population Health Sciences, Oregon State University, 103 Milam Hall, Corvallis, OR 97331; Linus Pauling Institute, Oregon State University, 307 Linus Pauling Science Center, Corvallis, OR 97331. Electronic address: Carmen.Wong@oregonstate.edu.
authors.forename: Carmen P
authors.initials: CP
authors.lastname: Wong
authors.affiliation: Center for Epigenetics & Disease Prevention, Institute of Biosciences & Technology, Texas A&M Health Science Center, 2121 W. Holcombe Blvd., Mail Stop 1201, Houston, TX 77030-3303. Electronic address: gjohnson@ibt.tamhsc.edu.
authors.forename: Gavin S
authors.initials: GS
authors.lastname: Johnson
authors.affiliation: Department of Botany and Plant Pathology, Oregon State University, 2082 Cordley Hall, Corvallis, OR 97331; Center for Genome Research and Biocomputing, Oregon State University, 3021 Agriculture and Life Sciences Building, Corvallis, OR 97331. Electronic address: changj@science.oregonstate.edu.
authors.forename: Jeff H
authors.initials: JH
authors.lastname: Chang
authors.affiliation: Department of Biomedical Sciences, College of Veterinary Medicine, Oregon State University, 105 Magruder Hall, Corvallis, OR 97331. Electronic address: Christiane.Loehr@oregonstate.edu.
authors.forename: Christiane V
authors.initials: CV
authors.lastname: Löhr
authors.affiliation: Linus Pauling Institute, Oregon State University, 307 Linus Pauling Science Center, Corvallis, OR 97331; Environmental and Molecular Toxicology, Oregon State University, 1007 Agriculture & Life Sciences Building, Corvallis, OR 97331. Electronic address: david.williams@oregonstate.edu.
authors.forename: David E
authors.initials: DE
authors.lastname: Williams
authors.affiliation: Center for Epigenetics & Disease Prevention, Institute of Biosciences & Technology, Texas A&M Health Science Center, 2121 W. Holcombe Blvd., Mail Stop 1201, Houston, TX 77030-3303. Electronic address: rdashwood@ibt.tamhsc.edu.
authors.forename: Roderick H
authors.initials: RH
authors.lastname: Dashwood
authors.affiliation: Department of Biochemistry and Biophysics, Oregon State University, 2011 Agriculture and Life Sciences Building, Corvallis, OR 97331; The School of Electrical Engineering and Computer Science, Oregon State University, 1148 Kelley Engineering Center, Corvallis, OR 97331. Electronic address: David.Hendrix@oregonstate.edu.
authors.forename: David A
authors.initials: DA
authors.lastname: Hendrix
authors.affiliation: Biological and Population Health Sciences, Oregon State University, 103 Milam Hall, Corvallis, OR 97331; Linus Pauling Institute, Oregon State University, 307 Linus Pauling Science Center, Corvallis, OR 97331; Center for Genome Research and Biocomputing, Oregon State University, 3021 Agriculture and Life Sciences Building, Corvallis, OR 97331; Moore Family Center, Oregon State University, 103 Milam Hall, Corvallis, OR 97331. Electronic address: Emily.Ho@oregonstate.edu.
authors.forename: Emily
authors.initials: E
authors.lastname: Ho
mesh_terms: D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D017879:Isothiocyanates / Q000494:pharmacology*; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D062085:RNA, Long Noncoding / Q000235:genetics*; D034741:RNA, Small Interfering; D013454:Sulfoxides
chemical_list: D016588:Anticarcinogenic Agents; D017879:Isothiocyanates; D062085:RNA, Long Noncoding; D034741:RNA, Small Interfering; D013454:Sulfoxides; C016766:sulforaphane
keywords: Chemoprevention; Diet–gene interactions; LINC01116; Long noncoding RNA; Prostate cancer; Sulforaphane