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

Abstract

Long non-coding 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 DMSO. 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 upregulated several genes including GAPDH (regulates glycolysis), MAP1LC3B2 (autophagy) and H2AFY (chromatin structure). A 4-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.

A novel lncRNA‐LINC01116 regulates tumorigenesis of glioma by targeting VEGFA

“…Additionally, enforced LINC01116 expression significantly increased tumorigenicity. These findings provide evidence that LINC01116 functions as a key mediator of cell cycle, proliferation, migration, invasion, tumorigenesis and angiogenesis, and thus represents a promising target for glioma treatment, while LINC01116 has just been reported to regulate the proliferation of prostate cancer cells in 2017 …”

Knockdown of LINC01116 inhibits cell migration and invasion in head and neck squamous cell carcinoma through epithelial‐mesenchymal transition pathway

“…Numerous studies in recent years have shown a significant correlation between lncRNAs and tumor development and progression, 17,18 and identification of novel lncRNA-based prognostic and therapeutic targets is currently a fervent topic in cancer research. 21 OSCC and NPC are the two main types of HNSCC, 22 and LINC01116 was dramatically upregulated in both types compared with the adjacent normal tissues. The microarray results were successfully F I G U R E 2 The expression level and prognostic significance of the identified lncRNAs in HNSCC.…”

“…To determine the biological significance of the aberrantly expressed lncRNAs in HNSCC, we analyzed two microarray datasets-GSE30784 and GSE29330from the GEO database and identified 21 overlapping lncRNAs, of which six were upregulated and 15 were downregulated. [19][20][21] To further dissect the underlying mechanism of the oncogenic role of LINC01116 in HNSCC, we mapped the functional networks of lncRNAs using circlncRNAnet, an integrated web-based resource, to screen for the coexpressing genes of LINC01116. Three overlapping upregulated lncRNAs and three overlapping downregulated lncRNAs were randomly selected to verify the integrated analysis results.…”

RNA-Sequencing Data Reveal a Prognostic Four-lncRNA-Based Risk Score for Bladder Urothelial Carcinoma: An in Silico Update

“…Primers used are as follows: AC145124.1, Forward-5′ -GGCTAACGTAGGCACTCTCG-3′, Reverse-5′-CACTTCTTCCACGAGCACCT-3′; AC010168.2, Forward-5′-TTGGTGTGCAGTTTGGTGTA-3′, Reverse-5′-TAAGTGGTCTGCCCATGTTT-3′; MIR200CHG, Forward-5′-CTGACCAACAACCTCTGACCTTCA-3′, Reverse-5′-AGGCAGCCATTTTGTCTCCTTC-3′; AC098613.1, Forward-5′-CAGGGAGGAAGGTATGTGGT-3′, Reverse-5′-ATCATGTAGGTGCAGGCAGA-3'; HIST4H4, Forward-5'-ATGTGGTGTACGCGCTGAAA-3', Reverse-5′-CGCCAAGTCTAATCCCGAGC-3′; GAPDH, Forward-5′-CTCCAAAATCAAGTGGGGCG-3′, Reverse-5′-TGGTTCACACCCATGACGAA-3′. Relative expression was determined by using the formula: Relative expression = 2 -(Cq gene -Cq GAPDH ) [40,41]. Analysis of the correlation between AC010168.2 and HIST4H4 expression was performed using SPSS 22.0 software.…”