Exosomes are small vesicles secreted by living cells, with a typical lipid bilayer structure. They carry a variety of proteins, lipids, RNA and other important information, play an important role in the transmission of substances and information between cells, and gradually become a marker for early diagnosis of many diseases and an important tool in drug delivery system. Immune cells are an important part of tumor microenvironment, and they can affect tumor progression by secreting a variety of immunoreactive substances. This review focuses on the effects of various immune cell-derived exosomes on tumor cells, different immune cells and other stromal cells in tumor microenvironment. Exosomes derived from different immune cells can not only reshape a pro-inflammatory microenvironment to inhibit tumor progression, but also promote tumor progression by inhibiting the killing effect of NK cells, CD8⁺T cells and other cells or promoting tumor cells and immunosuppressive immune cells. In addition, we also discussed that some exosomes derived from immune cells (such as DC, M1 macrophages and neutrophils) play a tumor inhibitory role after being engineered.

Backgrounds. The presence of amyloid deposits of human islet amyloid polypeptide (hIAPP) in islet β-cells has been associated with type 2 diabetes occurrence and islet graft failure. Self-assembly into oligomers and fibrils during the process of aggregation by hIAPP can lead to failure and depletion of β-cells. Studies have shown that some critical regions of hIAPP might contribute to the aggregation. Thus, many studies focused on finding the effective molecules, especially the short-peptide inhibitors, that bind to these regions and disrupt the aggregation of hIAPP. In the present study, a novel pentapeptide inhibitor Phe-Leu-Pro-Asn-Phe (FLPNF) was designed and its effectiveness on the inhibition of the formation of amyloid deposits was examined. Methods. The binding mode between FLPNF and hIAPP was performed using molecular docking. The effectiveness of FLPNF on inhibiting hIAPP amyloid aggregation was tested by Thioflavin T (ThT) staining. Furthermore, negative stain electron microscopy was used to observe hIAPP fibrils. A biolayer interferometry analysis was used to identify the interaction between FLPNF and hIAPP. In addition, the cytotoxicity toward INS-1 cells was tested by a cell proliferation assay. Results. FLPNF was predicted to have a compact conformation to bind at the site of hIAPP. FLPNF strongly inhibited the amyloid aggregation of hIAPP at a 10 : 1 molar ratio in vitro. Coincubation of FLPNF with hIAPP decreased the amount of hIAPP fibrils. Furthermore, a direct interaction between FLPNF and hIAPP was confirmed. FLPNF could also decrease the cytotoxic effect of hIAPP. Conclusions. The novel pentapeptide inhibitor FLPNF was constructed and inhibited the aggregation through direct binding to hIAPP. It is considered a suitable inhibitor for hIAPP amyloid deposit formation.

Background: Circular ribonucleic acids (circRNAs) are highly stable and conserved forms of RNAs present in all eukaryotes. They can modulate the expression of genes by sponging specific micro RNAs (miRNAs), thereby affecting various disease processes. However, their expression pattern in human breast cancer has not been elucidated. Methods: In this study, differentially expressed circRNAs in breast cancer tissues and paired noncancerous tissues were analyzed using an Arraystar Human circRNA Microarray, and hsa_circ_0006220 was selected for its 27-fold downregulation in breast cancer tissues. Its expression was also verified in 50 breast cancer and paired noncancerous tissues using real-time polymerase chain reaction (RT-PCR). An analysis of the expression of hsa_circ_0006220 and the clinicopathological factors in breast cancer was conducted. A receiver operating characteristic (ROC) curve of hsa_circ_0006220 was constructed. The interaction between hsa_circ_0006220 and five possible target miRNAs was predicted, and their expression were verified when overexpressing hsa_circ_0006220 by RT-PCR. Results: Hsa_circ_0006220 was found to be significantly downregulated in breast cancer tissues compared to the paired noncancerous tissues by microarray and RT-PCR. The expression of hsa_circ_0006220 was significantly inversely correlated with histological type (P=0.0028) and lymph node metastasis (P=0.0341). The area under the ROC curve (AUC) was 0.706. Five miRNAs that might be sponged by hsa_circ_0006220 were predicted. MiR-197-5p was significantly downregulated after overexpression of hsa_circ_0006220. Conclusions: Our results indicated that hsa_circ_0006220 may play a role in human breast cancer and might be a potential tumor marker for breast cancer screening.

Background: Breast cancer is one of the most significant causes of death in women around the world. Circular RNAs (circRNAs), which are a novel class of conserved RNA molecules, are involved in the occurrence and development of various diseases, especially malignancies; however, researchers rarely report their roles in human breast cancer. Methods: In the present study, the differentially expressed levels of circRNAs in human breast cancer tissues and paired noncancerous tissues were screened by circRNA microarray. Hsa_circ_0043278 was downregulated 43-fold in breast cancer and was selected for further analysis. The expression of hsa_circ_0043278 was verified in breast cancer specimens and paired noncancerous tissues by quantitative reverse transcription polymerized chain reaction (qRT-PCR) technique. The relationship between the expression of hsa_circ_0043278 and the clinicopathological features was analyzed. Results: Among the 520 differentially expressed circRNAs, 292 significantly upregulated circRNAs and 228 downregulated circRNAs in the breast cancer tissues compared with the paired noncancerous tissues. The area under the receiver operating characteristic (ROC) curve of hsa_circ_0043278 was 0.690. The results of the bioinformatics prediction showed five target miRNAs that might be sponged by hsa_circ_0043278. The expression of hsa_circ_0043278 was associated with lymph node metastasis and histological type of the patient. Patients with lymph node metastasis have tumors with significantly downregulated expression of hsa_circ_0043278 (P=0.0201). Conclusions: Our results suggest that hsa_circ_0043278 is downregulated and may play a key role in human breast cancer.

Aberrant DNA methylation is the most common type of epigenetic alteration and is associated with many types of cancer. Although previous studies have provided a few novel DNA methylation markers in hepatocellular carcinoma (HCC), specific DNA methylation patterns and comparisons of the aberrant alterations in methylation between HCC and normal liver cell lines have not yet been reported. Therefore, in the present study the Illumina Infinium HumanMethylation 450K BeadChip was employed to identify the genome‑wide aberrant DNA methylation profiles of Huh7 and L02 cells. Following Bonferroni adjustment, 102,254 differentially methylated CpG sites (covering 26,511 genes) were detected between Huh7 and L02 cells. Of those CpG sites, 62,702 (61.3%) sites were hypermethylated (covering 12,665 genes) and 39,552 (38.7%) sites were hypomethylated (covering 13,846 genes). The results of the present study indicated that 40.3% of the CpG sites were in CpG island regions, 20.7% were in CpG shores and 8.8% were in shelf regions. A total of 57.3% hypermethylated CpG sites and 39.4% of the hypomethylated CpG sites had a |β‑Difference| ≥50%. Within the significant differentially methylated CpG sites, 490 genes were located within 598 differentially methylated regions. Gene Ontology enrichment analysis revealed that 2,107 differentially methylated genes were associated with ‘biological process’, 13,351 differentially methylated genes were associated with ‘molecular function’, and 18,041 differentially methylated genes were associated with ‘cellular component’. Kyoto Encyclopedia of Genes and Genomes pathway‑based analysis revealed 43 signaling pathways that were associated with 5,195 differentially methylated genes. These results demonstrated that aberrant DNA methylation may be a key and common event underlying the tumorigenesis of Huh7 cells. The present study also identified many subsets of hypo‑ or hyper‑methylated CpG sites, genes and signaling pathways, which have an importance in the occurrence and development of HCC.