Recently, long non-coding RNAs (lncRNAs) have been shown to have important regulatory roles in human cancer biology. In our study, we found that lncRNA CCAT1, whose expression is significantly increased and is correlated with outcomes in Esophageal Squamous Cell Carcinoma (ESCC). Consecutive experiments confirmed that H3K27-acetylation could activate expression of colon cancer associated transcript-1 (CCAT1). Further experiments revealed that CCAT1 knockdown significantly repressed the proliferation and migration both in vitro and in vivo. RNA-seq analysis revealed that CCAT1 knockdown preferentially affected genes that are linked to cell proliferation, cell migration and cell adhesion. Mechanistic investigations found that CCAT1 could serve as a scaffold for two distinct epigenetic modification complexes (5΄ domain of CCAT1 binding Polycomb Repressive Complex 2 (PRC2) while 3΄ domain of CCAT1 binding SUV39H1) and modulate the histone methylation of promoter of SPRY4 (sprouty RTK signaling antagonist 4) in nucleus. In cytoplasm, CCAT1 regulates HOXB13 as a molecular decoy for miR-7, a microRNA that targets both CCAT1 and HOXB13, thus facilitating cell growth and migration. Together, our data demonstrated the important roles of CCAT1 in ESCC oncogenesis and might serve as targets for ESCC diagnosis and therapy.

BackgroundRecently, increasing evidence shows that long noncoding RNAs (lncRNAs) play a significant role in human tumorigenesis. However, the function of lncRNAs in human gastric cancer remains largely unknown.ResultsBy using publicly available expression profiling data from gastric cancer and integrating bioinformatics analyses, we screen and identify a novel lncRNA, HOXC-AS3. HOXC-AS3 is significantly increased in gastric cancer tissues and is correlated with clinical outcomes of gastric cancer. In addition, HOXC-AS3 regulates cell proliferation and migration both in vitro and in vivo. RNA-seq analysis reveals that HOXC-AS3 knockdown preferentially affects genes that are linked to proliferation and migration. Mechanistically, we find that HOXC-AS3 is obviously activated by gain of H3K4me3 and H3K27ac, both in cells and in tissues. RNA pull-down mass spectrometry analysis identifies that YBX1 interacts with HOXC-AS3, and RNA-seq analysis finds a marked overlap in genes differentially expressed after YBX1 knockdown and those transcriptionally regulated by HOXC-AS3, suggesting that YBX1 participates in HOXC-AS3-mediated gene transcriptional regulation in the tumorigenesis of gastric cancer.ConclusionsTogether, our data demonstrate that abnormal histone modification-activated HOXC-AS3 may play important roles in gastric cancer oncogenesis and may serve as a target for gastric cancer diagnosis and therapy.Electronic supplementary materialThe online version of this article (10.1186/s13059-018-1523-0) contains supplementary material, which is available to authorized users.

Breast cancer is a common malignancy in women. Acquisition of drug resistance is one of the main obstacles encountered in breast cancer therapy. Long non-coding RNA (lncRNA) has been demonstrated to play vital roles in both development and tumorigenesis. However, the relationship between lncRNAs and the development of chemoresistance is not well established. In the present study, the high expression of lncRNA H19 was identified as a powerful factor associated with paclitaxel (PTX) resistance in ERα-positive breast cancer cells, but not in ERα-negative breast cancer cells. LncRNA H19 attenuated cell apoptosis in response to PTX treatment by inhibiting transcription of pro-apoptotic genes BIK and NOXA. H19 was further confirmed to suppress the promoter activity of BIK by recruiting EZH2 and by trimethylating the histone H3 at lysine 27. Interestingly, our data showed that lncRNA H19 was one of the downstream target molecules of ERα. Altered ERα expression may therefore change H19 levels to modulate the apoptosis response to chemotherapy in breast cancer cells. Our data suggest that the ERα-H19-BIK signaling axis plays an important role in promoting chemoresistance.

Recently, long noncoding RNAs (lncRNAs) have been shown to have important regulatory roles in human cancer biology. By utilizing publicly available lncRNAs expression profiling data and integrating analyses, we screened out LINC00668, whose expression is significantly increased and correlated with outcomes in gastric cancer (GC). Further experiments revealed that LINC00668 knockdown significantly repressed proliferation, both in vitro and in vivo. Mechanistic investigations showed that LINC00668 was a direct transcriptional target of E2F transcription factor 1 (E2F1). We further demonstrated that LINC00668 was associated with PRC2 and that this association was required for epigenetic repression of cyclin-dependent protein kinase inhibitors (CKIs), including p15, p16, p21, p27 and p57, thus contributing to the regulation of the gastric cancer cell cycle. Our results suggest that E2F1-activated LINC00668, as a cell cycle regulator, enriches the mechanistic link between lncRNA and the E2F1-mediated cell cycle regulation pathway and may serve as a candidate prognostic biomarker and target for new therapies in human gastric cancer.

Listeria monocytogenes is an important foodborne pathogenic bacterium that is explicitly threatening public health and food safety. Rapid, simple, and sensitive detection methods for this pathogen are of urgent need for the increasing on-site testing demands. Application of the isothermal recombinase polymerase amplification (RPA) and the lateral flow strip (LFS) in the detection is promising for fast speed, high sensitivity, and little dependency on equipment and trained personnel. However, the simplicity comes with an intrinsic and non-negligible risk, the false-positive signals from primer-dimers. In this study, an improved RPA-LFS system was established for detection of L. monocytogenes that eliminated false-positive signals from primerdimers. Primer candidates were carefully selected from the entire L. monocytogenes genome sequence and rigorously screened for specific amplifications in PCR and RPA reactions. For the optimal primer pairs, probes that matched the targeted fragment sequences, although had the smallest chance to form cross-dimers with the primers, were designed and screened. The intelligent use of the probe successfully linked the positive signal to the actual amplification product. This RPA-LFS system was highly specific to L. monocytogenes and was able to detect as low as 1 colony-forming unit of the bacterium per reaction (50 µl) without DNA purification, or 100 fg of the genomic DNA/50 µl. The amplification could be conducted under the temperature between 37 and 42 • C, and the whole detection finished within 25 min. Test of artificially contaminated milk gave 100% accuracy of detection without purification of the samples. Various food samples spiked with 10 colony-forming unit of L. monocytogenes per 25 g or 25 ml were successfully detected after an enrichment time period of 6 h. The RPA-LFS system established in this study is a rapid, simple, and specific detection method for L. monocytogenes that has eliminated false-positive results from primer-dimers. In

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Background: Vibrio alginolyticus is an important pathogen that has to be closely monitored and controlled in the mariculture industry because of its strong pathogenicity, quick onset after infection and high mortality rate in aquatic animals. Fast, simple and specific methods are needed for on-site detection to effectively control outbreaks and prevent economic losses. The detection specificity towards the pathogenic strains has to be emphasized to facilitate pointed treatment and prevention. Polymerase chain reaction (PCR)-based molecular approaches have been developed, but their application is limited due to the requirement of complicated thermal cycling machines and trained personnel. Results: A fast, simple and highly specific detection method for V. alginolyticus pathogenic strains was established based on isothermal recombinase polymerase amplification (RPA) and lateral flow dipsticks (LFD). The method targeted the virulence gene toxR, which is reported to have good coverage for V. alginolyticus pathogenic strains. To ensure the specificity of the method, the primer-probe set of the RPA system was carefully designed to recognize regions in the toxR gene that diverge in different Vibrio species but are conserved in V. alginolyticus pathogenic strains. The primer-probe set was determined after a systematic screening of amplification performance, primer-dimer formation and false positive signals. The RPA-LFD method was confirmed to have high specificity for V. alginolyticus pathogenic strains without any cross reaction with other Vibrio species or other pathogenic bacteria and was able to detect as little as 1 colony forming unit (CFU) per reaction without DNA purification, or 170 fg of genomic DNA, or 6.25 × 10 3 CFU/25 g in spiked shrimp without any enrichment. The method finishes detection within 30 min at temperatures between 35°C and 45°C, and the visual signal on the dipstick can be directly read by the naked eye. In an application simulation, randomly spiked shrimp homogenate samples were 100% accurately detected.

Drug-induced aberrant DNA methylation is the first identified epigenetic marker involved in chemotherapy resistance. Understanding how the aberrant DNA methylation is acquired would impact cancer treatment in theory and practice. In this study we systematically investigated whether and how ERα propelled aberrant global DNA hypermethylation in the context of breast cancer drug resistance. Our data demonstrated that anticancer drug paclitaxel (PTX) augmented ERα binding to the DNMT1 and DNMT3b promoters to activate DNMT1 and DNMT3b genes, enhancing the PTX resistance of breast cancer cells. In support of these observations, estrogen enhanced multi-drug resistance of breast cancer cells by up-regulation of DNMT1 and DNMT3b genes. Nevertheless, the aberrant global DNA hypermethylation was dominantly induced by ERα-activated-DNMT1, since DNMT1 over-expression significantly increased global DNA methylation and DNMT1 knockdown reversed the ERα-induced global DNA methylation. Altering DNMT3b expression had no detectable effect on global DNA methylation. Consistently, the expression level of DNMT1 was positively correlated with ERα in 78 breast cancer tissue samples shown by our immunohistochemistry (IHC) analysis and negatively correlated with relapse-free survival (RFS) and distance metastasis-free survival (DMFS) of ERα-positive breast cancer patients. This study provides a new perspective for understanding the mechanism underlying drug-resistance-facilitating aberrant DNA methylation in breast cancer and other estrogen dependent tumors.