Conventional tumor markers for non-invasive diagnosis of gastric cancer (GC) exhibit insufficient sensitivity and specificity to facilitate detection of early gastric cancer (EGC). We aimed to identify EGC-specific exosomal lncRNA biomarkers that are highly sensitive and stable for the non-invasive diagnosis of EGC. Hence, in the present study, exosomes from the plasma of five healthy individuals and ten stage I GC patients and from culture media of four human primary stomach epithelial cells and four gastric cancer cells (GCCs) were isolated. Exosomal RNA profiling was performed using RNA sequencing to identify EGC-specific exosomal lncRNAs. A total of 79 and 285 exosomal RNAs were expressed at significantly higher levels in stage I GC patients and GCCs, respectively, than that in normal controls. Through combinational analysis of the RNA sequencing results, we found two EGC-specific exosomal lncRNAs, lncUEGC1 and lncUEGC2, which were further confirmed to be remarkably up-regulated in exosomes derived from EGC patients and GCCs. Furthermore, stability testing demonstrates that almost all the plasma lncUEGC1 was encapsulated within exosomes and thus protected from RNase degradation. The diagnostic accuracy of exosomal lncUEGC1 was evaluated, and lncUEGC1 exhibited AUC values of 0.8760 and 0.8406 in discriminating EGC patients from healthy individuals and those with premalignant chronic atrophic gastritis, respectively, which was higher than the diagnostic accuracy of carcinoembryonic antigen. Consequently, exosomal lncUEGC1 may be promising in the development of highly sensitive, stable, and non-invasive biomarkers for EGC diagnosis.Electronic supplementary materialThe online version of this article (10.1186/s12943-018-0834-9) contains supplementary material, which is available to authorized users.
SummaryWnt signalling through b-catenin and the lymphoid-enhancing factor 1/T-cell factor (LEF1/TCF) family of transcription factors maintains stem cell properties in both normal and malignant tissues; however, the underlying molecular pathway involved in this process has not been completely defined. Using a microRNA microarray screening assay, we identified let-7 miRNAs as downstream targets of the Wnt-b-catenin pathway. Expression studies indicated that the Wnt-b-catenin pathway suppresses mature let-7 miRNAs but not the primary transcripts, which suggests a post-transcriptional regulation of repression. Furthermore, we identified Lin28, a negative let-7 biogenesis regulator, as a novel direct downstream target of the Wnt-b-catenin pathway. Loss of function of Lin28 impairs Wnt-bcatenin-pathway-mediated let-7 inhibition and breast cancer stem cell expansion; enforced expression of let-7 blocks the Wnt-b-catenin pathway-stimulated breast cancer stem cell phenotype. Finally, we demonstrated that the Wnt-b-catenin pathway induces Lin28 upregulation and let-7 downregulation in both cancer samples and mouse tumour models. Moreover, the delivery of a modified lin28 siRNA or a let-7a agomir into the premalignant mammary tissues of MMTV-wnt-1 mice resulted in a complete rescue of the stem cell phenotype driven by the Wnt-b-catenin pathway. These findings highlight a pivotal role for Lin28/let-7 in Wnt-b-catenin-pathwaymediated cellular phenotypes. Thus, the Wnt-b-catenin pathway, Lin28 and let-7 miRNAs, three of the most crucial stem cell regulators, connect in one signal cascade.
This paper proposes an image encryption algorithm based on a chaotic map and information entropy. Unlike Fridrich’s structure, the proposed method contains permutation, modulation, and diffusion (PMD) operations. This method avoids the shortcoming in traditional schemes of strictly shuffling the pixel positions before diffusion encryption. Information entropy is employed to influence the generation of the keystream. The initial keys used in the permutation and diffusion stages interact with each other. As a result, the algorithm acts as an indivisible entity to enhance security. Experimental results and security analyses demonstrate the good performance of the proposed algorithm as a secure and effective communication method for images.
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