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BACKGROUND: Triple-negative breast cancer (TNBC) is a type of highly invasive breast cancer with poor prognosis. Recently, massive data reveal that long non-coding RNAs (lncRNAs) play important roles in cancer progress. Recently, although the role of lncRNAs in breast cancer has been well documented, few focused on TNBC. In this study, we aimed to systematically identify functional lncRNAs and to explore its molecular mechanism on TNBC progress. METHODS: The recurrence of lncRNAs and their target genes were validated with TNBC biopsies and cell lines. Total one hundred and thirteen TNBC biopsies, including nineteen patient-matched samples, were collected. The profile of TNBC-related lncRNAs and their target genes were characterized by RNA sequencing (RNA-seq) and bioinformatic analysis. Tumor specific lncRNAs, which also showed biological function correlated with TNBC, were identified as potential candidates; and the target genes, which regulated by the identified lncRNAs, were predicted by the analysis of expression correlation and chromosome colocalization. Cross bioinformatic validation was performed with TNBC independent datasets from the cancer genome atlas (TCGA). The biological functions and molecular mechanism were investigated in TNBC model cell lines by cell colony forming assay, flow cytometry assay, western-blot, RNA Fluorescence in situ Hybridization assay (RNA FISH) and chromatin immunoprecipitation-qPCR (ChIP-qPCR). RESULTS: Abundant Lnc-BTG3-7:1, which targets gene C21ORF91, was specifically observed in TNBC biopsies and cell lines. Knockdown of Lnc-BTG3-7:1 or C21ORF91 strongly inhibited cell proliferation, promoted cell apoptosis and cell cycle G1-arrested. Meanwhile, investigation of molecular mechanism indicated that Lnc-BTG3-7:1, cooperated with transcription factor JUND, cis-regulated the transcription of C21ORF91 gene, and down-regulation of Lnc-BTG3-7:1/C21ORF91 suppressed GRB2-RAS-RAF-MEK-ERK and GRB2-PI3K-AKT-GSK3ß-ß-catenin pathways. CONCLUSIONS: In this study, we identified a TNBC specific lncRNA Lnc-BTG3-7:1, which sustained tumor progress. Up-regulation of Lnc-BTG3-7:1 promoted the transcription of oncogene C21ORF91 and activated PI3K-AKT-GSK3ß-ß-catenin and MAPK pathways. Taken together, our results not only identified a biomarker for diagnosis but also provided a potential therapeutic target against TNBC.
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Objective To study whether citrate lock is superior to heparin lock in the prevention of catheter related infections,bleeding complications and catheter malfunctions among hemodialysis patients with tunneled catheters.Methods By searching in Pubmed,the Cochrane Library,EMBASE,Ovid,WanFang,VIP,CNKI and CBM databases as well as related journals,qualified randomized controlled trials were included in a Meta-analysis using Revman 5.0 and STATA 10.0 software.The endpoints included catheter related infection,bleeding complication,thrombolytic treatment,catheter removal for malfunction,catheter thrombosis and all-cause death.Results Fifteen randomized controlled trials were included with 1621 patients involved.Eight studies compared citrate alone with heparin lock,while 7 trials focused on citrate in combination with other antimicrobials.Pooled analysis demonstrated that incidence of catheter related infections in patients receiving citrate lock decreased by 47％ compared with those on heparin (RR=0.53,95％CI 0.36-0.77,P ＜ 0.01).Subgroup analysis by types of citrate lock indicated that all combined lock solutions of citrate and other antimicrobials (citrate + gentamicin,citrate + taurolidine,citrate + methylene blue +methylparaben + propylparaben) were superior to heparin lock in preventing catheter-related infections (P =0.01,0.04,0.01,respectively); citrate alone seemed to reduce catheter-related infection risk (RR =0.68),but no statistically significant difference was observed (95％CI 0.38-1.21,P=0.19).There were fewer patients with bleeding complications in citrate group (RR =0.53,95％ CI 0.34-0.S4,P ＜ 0.01),while citrate showed no advantage over heparin lock in terms of thrombolytic treatment (P =0.93),catheter removal for malfunction (P =0.35),catheter thrombosis (P =0.64) and all-cause death (P =0.35).Conclusions For hemodialysis patients with tunneled catheters,combined lock solutions of citrate and other antimicrobials,rather than citrate alone,are superior to heparin in preventing catheter related infections.Citrate locks are associated with less bleeding complications,and are comparable to heparin in the maintenance of catheter patency.
