• Esophageal carcinoma
• Factors
• Machine learning
• Predictive model
• Survival rate

• cancer-suppressing
• cancer‑promoting
• regulatory factor
• salt‑induced kinase 1
• signal channel

• Humans
• Protein Serine-Threonine Kinases/metabolism
• Neoplasms/drug therapy
• Neoplasms/metabolism
• Neoplasms/genetics
• Signal Transduction/drug effects
• Molecular Targeted Therapy/methods
• Animals
• Gene Expression Regulation, Neoplastic

• cancer treatment
• salt inducible kinase
• tumor inhibitor
• tumor promoter
• tumorigenesis

• Humans
• Oncogenes
• Neoplasms/genetics
• AMP-Activated Protein Kinases
• Cell Transformation, Neoplastic

• Cancers
• HEIH
• Therapeutic target
• lncRNA

• 2017NJMU059 nanjing medical university science and technology development foundation

• China's coastal waters
• Harmful algal blooms
• Meta-omics
• Omics

• China
• Ecosystem
• Forecasting
• Harmful Algal Bloom

Increasing evidence suggests a role of epigenetic mechanisms at chromosome 8q24, an important cancer genetic susceptibility region, in prostate cancer. We investigated whether MYC DNA methylation at 8q24 (six CpG sites from exon 3 to the 3′ UTR) in prostate tumor was associated with tumor aggressiveness (based on Gleason score, GS), and we incorporated RNA expression data to investigate the function. We accessed radical prostatectomy tissue for 50 Caucasian and 50 African American prostate cancer patients at the University of Maryland Medical Center, selecting an equal number of GS 6 and GS 7 cases per group. MYC DNA methylation was lower in tumor than paired normal prostate tissue for all six CpG sites (median difference: −14.74 to −0.20 percentage points), and we observed similar results for two nearby sites in The Cancer Genome Atlas (p < 0.0001). We observed significantly lower methylation for more aggressive (GS 7) than less aggressive (GS 6) tumors for three exon 3 sites (for CpG 212 (chr8:128753145), GS 6 median = 89.7%; GS 7 median = 85.8%; p-value = 9.4 × 10⁻⁴). MYC DNA methylation was not associated with MYC expression, but was inversely associated with PRNCR1 expression after multiple comparison adjustment (q-value = 0.04). Findings suggest that prostate tumor MYC exon 3 hypomethylation is associated with increased aggressiveness.

• DNA methylation
• Gleason score (GS)
• MYC
• RNA expression
• aggressive disease
• non-coding RNAs (ncRNAs)
• prostate cancer
• tumor tissue biomarkers

• Long non-coding RNAs
• cancer
• cell cycle regulation
• epigenetics
• genomic imprinting
• mammalian transcriptome.

FAM84B is a risk gene in breast and prostate cancers. Its upregulation is associated with poor prognosis of prostate cancer, breast cancer, and esophageal squamous cell carcinoma. FAM84B facilitates cancer cell proliferation and invasion in vitro, and xenograft growth in vivo. The FAM84B and Myc genes border a 1.2 Mb gene desert at 8q24.21. Co-amplification of both occurs in 20 cancer types. Mice deficient of a 430 Kb fragment within the 1.2 Mb gene desert have downregulated FAM84B and Myc expressions concurrent with reduced breast cancer growth. Intriguingly, Myc works in partnership with other oncogenes, including Ras. FAM84B shares similarities with the H-Ras-like suppressor (HRASLS) family over their typical LRAT (lecithin:retinal acyltransferase) domain. This domain contains a catalytic triad, H23, H35, and C113, which constitutes the phospholipase A_1/2 and O-acyltransferase activities of HRASLS1-5. These enzymatic activities underlie their suppression of Ras. FAM84B conserves H23 and H35 but not C113 with both histidine residues residing within a highly conserved motif that FAM84B shares with HRASLS1-5. Deletion of this motif abolishes FAM84B oncogenic activities. These properties suggest a collaboration of FAM84B with Myc, consistent with the role of the gene desert in strengthening Myc functions. Here, we will discuss recent research on FAM84B-derived oncogenic potential.

• 8q24.21 gene desert
• FAM84B
• H-Ras-like suppressor (HRASLS)
• Myc
• Ras
• tumorigenesis

• Breast Neoplasms/genetics
• Breast Neoplasms/pathology
• Cell Proliferation/genetics
• Chromosomes, Human, Pair 8/genetics
• Female
• Gene Expression Regulation, Neoplastic/genetics
• Humans
• Male
• Membrane Proteins/genetics
• Neoplasm Invasiveness/genetics
• Neoplasm Invasiveness/pathology
• Neoplasm Proteins/genetics
• Prostatic Neoplasms/genetics
• Prostatic Neoplasms/pathology

• Endometrial cancer
• HEIH
• MAPK signaling pathway
• Paclitaxel resistance

SNW1 is a nuclear receptor co-activator involved in splicing and transcription control, including androgen receptor signaling. Overexpression of SNW1 has been linked to adverse prognosis in different cancer types, but studies on the role of SNW1 in prostate cancer are lacking.

Using immunohistochemistry, we analyzed SNW1 expression in 10,310 prostate cancers in a tissue microarray (TMA) with attached clinical and molecular data.

The comparison with normal prostate tissue revealed an up regulation of SNW1 in a subset of cancer samples. SNW1 staining was considered weak in 31.5%, moderate in 37.7% and strong in 14% of cancers. Strong SNW1 expression was markedly more frequent in prostate cancers harboring the TMPRSS2:ERG fusion (24%) than in ERG negative cancers (7%, p < 0.0001). Significant associations with Gleason grade, stage, nodal status and early biochemical recurrence were observed in the ERG negative and positive subset. Multivariable modeling revealed that the prognostic value of SNW1 up regulation was independent from the established preoperative histopathological and clinical parameters.

These results demonstrate that SNW1 overexpression is an independent prognostic marker in prostate cancer with potential clinical utility.

The online version of this article (10.1186/s13000-019-0810-8) contains supplementary material, which is available to authorized users.

• Prognosis
• Prostate cancer
• SKIP1
• SNW1
• TMPRSS2:ERG

Microtubule-associated protein Tau (MAPT) overexpression has been linked to poor prognosis and decreased response to taxane-based therapies in several cancer types, but its relevance in prostate cancer is unknown.

In this study, MAPT expression was analyzed by immunohistochemistry on a tissue microarray containing 17,747 prostate cancers.

MAPT was absent in normal prostate epithelial cells but detectable in 1004 (8.2%) of 12,313 interpretable cancers. Its expression was associated with advanced tumor stage, high Gleason grade, positive lymph nodes, and early biochemical recurrence (p < 0.0001 each). For example, MAPT was found in 3.6% of 2072 Gleason ≤3 + 3 cancers but in 14.4% of 704 Gleason ≥4 + 4 cancers. High-level MAPT staining was also linked to TMPRSS2:ERG fusions (p < 0.0001). MAPT staining was seen in 15.2 and 16% of cancers with TMPRSS2:ERG fusion detected by immunohistochemistry and fluorescence in-situ hybridization, but in only 3.5 and 3.9% of cancers without ERG staining or ERG rearrangements. Moreover, an association was found between MAPT expression and PTEN deletions, with 19% MAPT positivity in 948 PTEN deleted cancers but only 7% MAPT positivity in 3895 tumors with normal PTEN copy numbers (p < 0.0001). Multivariate analysis revealed that the prognostic value of MAPT was independent from established parameters. Conventional large section analyses showed intratumoral MAPT heterogeneity in all three analyzed cancers.

The results of our study identify MAPT, as a moderate prognostic marker in prostate cancer, whose clinical impact, however, may be limited due to the rarity and heterogeneity of its expression.

The online version of this article (10.1186/s12885-019-5390-1) contains supplementary material, which is available to authorized users.

• Deletion
• ERG
• MAPT
• PTEN
• Prostate cancer
• Tau

The chromosome 8q24.21 locus, which contains the proto-oncogene c-MYC, long non-coding RNA PVT1, and microRNAs (miRs), is the most commonly amplified region in human prostate cancer. A long-range interaction of genetic variants with c-MYC or long non-coding PVT1 at this locus contributes to the genetic risk of prostate cancer. At this locus is a cluster of genes for six miRs (miR-1204, −1205, −1206, −1207–3p, −1207–5p, and −1208), but their functional role remains elusive. Here, the copy numbers and expressions of miRs-1204~1208 were investigated using quantitative PCR for prostate cancer cell lines and primary tumors. The data revealed that copy numbers and expression of miR-1205 were increased in both castration-resistant prostate cancer cell lines and in primary tumors. In castration-resistant prostate cancer specimens, the copy number at the miR-1205 locus correlated with expression of miR-1205. Furthermore, functional analysis with an miR-1205 mimic, an miR-1205 inhibitor, and CRISPR/Cas9 knockout revealed that, in human prostate cancer cells, miR-1205 promoted cell proliferation and cell cycle progression and inhibited hydrogen peroxide-induced apoptosis. In these cells, miR-1205 downregulated expression of the Egl-9 family hypoxia inducible factor 3 (EGLN3) gene and targeted a site in its 3’-untranslated region to downregulate its transcriptional activity. Thus, by targeting EGLN3, miR-1205 has an oncogenic role and may contribute to the genetic risk of castration-resistant prostate cancer.

• laryngeal squamous cell carcinoma
• long noncoding RNA PVT1
• miR-519d-3p

• BRCA2 Protein/genetics
• Cell Cycle Proteins/genetics
• Checkpoint Kinase 2/genetics
• Colorectal Neoplasms, Hereditary Nonpolyposis/complications
• Colorectal Neoplasms, Hereditary Nonpolyposis/genetics
• DNA Repair
• Early Detection of Cancer
• Genetic Predisposition to Disease
• Genome-Wide Association Study
• Germ-Line Mutation
• Homeodomain Proteins/genetics
• Humans
• Male
• Molecular Targeted Therapy
• Nuclear Proteins/genetics
• Polymorphism, Single Nucleotide
• Prostate-Specific Antigen/blood
• Prostatic Neoplasms/genetics
• Prostatic Neoplasms/pathology
• Prostatic Neoplasms/therapy
• Ubiquitin-Protein Ligases/genetics

• 17528 Cancer Research UK

The role of many lncRNAs in cancer remains elusive including that for a Prostate Cancer Associated Transcript 92 (PCAT92). PCAT92 shares the locus on chromosome 13 with ABCC4 gene, known to be implicated in prostate cancer. It has been shown that PCAT92 and ABCC4 are up-regulated in prostate cancer samples from multiple transcriptome datasets. Among the prostate cancer cell-lines LNCaP showed maximum overexpression of PCAT92 compared to control cell-line RWPE-1. We have shown that knockdown of PCAT92 in LNCaP cells reduces cell viability and proliferation and down-regulates ABCC4 transcript/protein expression. The shared region between PCAT92 and ABCC4 has a binding site for an oncogenic transcription factor (ZIC2) which is also upregulated in the majority of datasets studied here. ZIC2 binding to the predicted ABCC4 promoter has been confirmed using pull-down assay. Interestingly, under PCAT92 knockdown condition, there is a reduction in the ZIC2 binding to ABCC4 promoter indicating the potential involvement of PCAT92 in the recruitment of ZIC2. We have identified distinct regions on PCAT92 with potential to bind to ZIC2 non-DNA binding Zinc-finger domain and potential for triplex formation near ABCC4 promoter region, which have been experimentally validated. Together, these observations and localization in the nucleus suggests that PCAT92 may play a role in prostate cancer by increasing the local concentration of ZIC2 by forming RNA-DNA triplex near ABCC4 promoter thus helping in recruitment of ZIC2 for ABCC4 regulation.

• ABCC4
• PCAT92
• ZIC2
• lncRNA
• prostate cancer

Long non-coding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1) has been reported to be overexpressed in prostate cancer cells and associated with tumorigenesis in various types of cancer. However, the biological function of lncRNA PVT1 remains largely unknown. The aim of the present study was to investigate the effect of lncRNA PVT1 expression on the proliferation and migration of prostate cancer cells. Stably transfected prostate cancer cells with downregulated expression of lncRNA PVT1 were constructed by an efficient siRNA fragment, followed by confirmation by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Proliferation was assessed using CCK-8, colony formation and xenograft assays, and cell migration was evaluated using a wound healing assay. The PathScan^® Intracellular Signaling Array kit was utilized to explore the underlying molecular mechanisms of lncRNA PVT1 expression in prostate cancer cells. RT-qPCR results confirmed that the lncRNA PVT1 expression level was successfully knocked down in prostate cancer cells. When lncRNA PVT1 expression was downregulated in prostate cancer cells, proliferation and migration were significantly inhibited, compared with the control lncRNA PVT1 group. Furthermore, PVT1 knockdown decreased the phosphorylation of p38 in DU145 cells. Therefore, the present study demonstrated that lncRNA PVT1 downregulation inhibits the proliferation and migration of prostate cancer cells, and is associated with p38 phosphorylation.

• RNA
• cell movement
• long noncoding
• proliferation
• prostatic neoplasms

Discussions regarding the correlations between long non-coding RNAs (lncRNAs) and cancers have dominated research in recent years. SIK1-LNC, a type of lncRNA and adjacent to salt-inducible kinases 1 (SIK1), has been found aberrantly expressed in lung cancer. However, its functional role in lung cancer remains largely unknown.

In this study, we aimed to explore the association between SIK1-LNC expression and SIK1 in lung cancer cells and further identify the impact of SIK1-LNC on the proliferation, migration invasion of lung cancer cells.

Of the 30 patients with non-small-cell lung carcinoma from Zhongnan Hospital of Wuhan University, RT-qPCR was performed to detect SIK1 and SIK1-LNC expressions in patients’ samples. Overexpression and knockdown experiments were conducted to analyze the SIK1 and SIK1-LNC expressions in lung cancer cell lines. CCK-8, Brdu, scratch wound-healing, and Transwell assays were respectively employed to evaluate the proliferative, migrative, and invasive abilities of lung cancer cells.

Both SIK1-LNC and SIK1 expression levels were evidently downregulated in 30 lung cancer tissues. SIK1-LNC expression was bound up with clinicopathologic features, including lymph node metastasis and distant metastasis. SIK1 expression showed a positive tendency with SIK1-LNC expression in lung cancer cells. SIK1-LNC exerted a significant repression on cell proliferatiive, miogrative and invasive abilities of lung cancer cells.

Our findings suggested that SIK1-LNC may act as a novel biomarker and therapeutic target for lung cancer.

• SIK1
• SIK1-LNC
• invasion
• lung cancer
• metastasis
• proliferation

Development of particular structures and proper functioning of the placenta are under the influence of sophisticated pathways, controlled by the expression of substantial genes that are additionally regulated by long non-coding RNAs (lncRNAs). To date, the expression profile of lncRNA in human term placenta has not been fully established. This study was conducted to characterize the lncRNA expression profile in human term placenta and to verify whether there are differences in the transcriptomic profile between the sex of the fetus and pregnancy multiplicity. RNA-Seq data were used to profile, quantify, and classify lncRNAs in human term placenta. The applied methodology enabled detection of the expression of 4463 isoforms from 2899 annotated lncRNA loci, plus 990 putative lncRNA transcripts from 607 intergenic regions. Those placentally expressed lncRNAs displayed features such as shorter transcript length, longer exon length, fewer exons, and lower expression levels compared to messenger RNAs (mRNAs). Among all placental transcripts, 175,268 were classified as mRNAs and 15,819 as lncRNAs, and 56,727 variants were discovered within unannotated regions. Five differentially expressed lncRNAs (HAND2-AS1, XIST, RP1-97J1.2, AC010084.1, TTTY15) were identified by a sex-bias comparison. Splicing events were detected within 37 genes and 4 lncRNA loci. Functional analysis of cis-related potential targets for lncRNAs identified 2021 enriched genes. It is presumed that the obtained data will expand the current knowledge of lncRNAs in placenta and human non-coding catalogs, making them more contemporary and specific.

• high-throughput RNA sequencing (RNA-Seq)
• human
• long non-coding RNA (lncRNA)
• placenta
• pregnancy
• transcriptome

• Computational Biology
• Exons/genetics
• Female
• Humans
• Placenta/metabolism
• Pregnancy
• RNA, Long Noncoding/genetics
• RNA, Messenger/genetics
• Sequence Analysis, RNA

Cell signaling events triggered by androgen hormone in prostate cells is dependent on activation of the androgen receptor (AR) transcription factor. Androgen hormone binding to AR promotes its displacement from the cytoplasm to the nucleus and AR binding to DNA motifs, thus inducing activatory and inhibitory transcriptional programs through a complex regulatory mechanism not yet fully understood. In this work, we performed RNA-seq deep-sequencing of LNCaP prostate cancer cells and found over 7000 expressed long intergenic non-coding RNAs (lincRNAs), of which ∼4000 are novel lincRNAs, and 258 lincRNAs have their expression activated by androgen. Immunoprecipitation of AR, followed by large-scale sequencing of co-immunoprecipitated RNAs (RIP-Seq) has identified in the LNCaP cell line a total of 619 lincRNAs that were significantly enriched (FDR < 10%, DESeq2) in the anti-Androgen Receptor (antiAR) fraction in relation to the control fraction (non-specific IgG), and we named them Androgen-Receptor-Associated lincRNAs (ARA-lincRNAs). A genome-wide analysis showed that protein-coding gene neighbors to ARA-lincRNAs had a significantly higher androgen-induced change in expression than protein-coding genes neighboring lincRNAs not associated to AR. To find relevant epigenetic signatures enriched at the ARA-lincRNAs’ transcription start sites (TSSs) we used a machine learning approach and identified that the ARA-lincRNA genomic loci in LNCaP cells are significantly enriched with epigenetic marks that are characteristic of in cis enhancer RNA regulators, and that the H3K27ac mark of active enhancers is conspicuously enriched at the TSS of ARA-lincRNAs adjacent to androgen-activated protein-coding genes. In addition, LNCaP topologically associating domains (TADs) that comprise chromatin regions with ARA-lincRNAs exhibit transcription factor contents, epigenetic marks and gene transcriptional activities that are significantly different from TADs not containing ARA-lincRNAs. This work highlights the possible involvement of hundreds of lincRNAs working in synergy with the AR on the genome-wide androgen-induced gene regulatory program in prostate cells.

• LNCaP prostate cancer cell line
• androgen receptor
• androgen receptor associated lincRNAs
• epigenetic marks
• genome-wide profiling
• long intergenic non-coding RNAs
• machine learning
• random forest algorithm

转录组是特定的细胞或组织在特定的时间或状态下转录出来的RNA集合, 转录组研究能够从整体水平研究基因功能以及基因结构, 并能很好的显示处于表达状态的基因数量和活跃程度. 作为转录组学新一代高通量测序技术之一, RNA-Seq技术能够更为快速、准确地为人们提供更多的生物体转录信息, 在生物医学研究中已经得到广泛应用. 随着全球胃肠肿瘤发病率的逐年提高, RNA-Seq技术在胃肠肿瘤研究领域进行全转录组测序分析的应用越来越多, 并取得了一些新的进展. 本文将就RNA-Seq技术原理、优势及其在胃肠肿瘤研究中的具体应用进行论述.

• 转录组学
• RNA-Seq
• 胃肠肿瘤

• Alu
• GWAS
• causative variant
• interspersed repeats
• structural variant

• PCGEM1
• alternative splicing
• androgen receptor
• breast cancer
• prostate cancer

• PVT1
• bladder cancer
• lncRNAs
• synthetic biology
• tetracycline-inducible

• Adult
• Aged
• Aged, 80 and over
• Apoptosis/genetics
• Cell Line
• Cell Line, Tumor
• Cell Proliferation/genetics
• Female
• Gene Expression Regulation, Neoplastic/drug effects
• Gene Expression Regulation, Neoplastic/genetics
• Humans
• Male
• Middle Aged
• Neoplasm Grading
• Neoplasm Staging
• RNA, Long Noncoding/genetics
• RNA, Small Interfering/genetics
• Reverse Transcriptase Polymerase Chain Reaction
• Tetracycline/pharmacology
• Up-Regulation
• Urinary Bladder Neoplasms/genetics
• Urinary Bladder Neoplasms/pathology

• Androgen receptor
• KLK
• PCA3
• PSA
• kallikrein-related peptidase
• miRNA
• prognosis
• prostate carcinoma
• prostate-specific antigen
• tumor marker