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Objective: To explore the targeting relationship between miRNA and epigenetic factors related to the prognosis of hepatocellular carcinoma (HCC), and to identify the potential impact of miRNA targeted epigenetic factors on the prognosis of HCC. Methods: The mRNA and miRNA sequencing data of all HCC samples were downloaded from the tumor Genome Atlas (TCGA) database, and the R program was used to analyze the difference of the sequencing data. The data of survival time, survival status and differential expression of miRNA were combined, and the risk score model of miRNA was constructed by univariate and multivariate Cox regression. The miRNA target genes and all the corresponding Epigenetic factors were predicted, and the differentially expressed Epigenetic factors (DEEFs) were screened. Then, the regulatory network of miRNA targeting deefs was established, the apparent factors in the network were enriched and analyzed, and the core genes in the protein-protein interaction (PPI) network and selection network were constructed. Finally, the relationship between the apparent factors and the prognosis of patients was analyzed and verified by Kaplan Meier (K-M) method. Results: 305 differentially expressed miRNAs were identified using EDGE algorithm. After Cox analysis, hsa-miR-139-5p, hsa-miR-101-3p and hsa-miR-7-5p (miR-139-5p, miR-101-3p and miR-7-5p) were finally screened as the Overall survival of HCC patients (Overall survival, OS). In addition, 34 DEEFs targeted by miRNAs were identified, among which EZH2, PKM, HJURP and CHEK1 had a significant impact on the survival of hepatocellular carcinoma. Conclusion: In this study, we successfully established a prognostic model of hepatocellular carcinoma miRNA-targeted epigenetics, and screened out epigenetic factors that are significantly related to the prognosis of hepatocellular carcinoma. It provides new potential prognostic biomarkers and therapeutic targets for HCC treatment, and lays a theoretical foundation for the follow-up basic research of HCC. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effects of exosomes derived from tumor-associated macrophages (TAMs) on migration and invasion of MDA-MB-231 cells in triple negative breast cancer. Methods: The MDA-MB-231 cells, a human breast cancer cell line, were divided into the experimental group and the blank control group. The exosomes were isolated from the supernatant of human peripheral blood mononuclear cells (THP-1) by a multi-step ultracentrifugal procedure. The effects of exosomes on migration and invasion of MDAMB-231 cells were studied by endocytosis assay of exosomes, Transwell migration assay and Celigo scratch assay. Results: Exosomes were ingested and endocytosed by MDAMB-231 cells, brought into the cytoplasm at 3h and enriched significantly at 6h. Compared with the blank control group, the number of metastatic cells in the Transwell compartment (241±3.35) and its variation relative to normal cells (144±2.33) in the experimental group were significantly increased (P<0.05). The 24 h migration rate of MDA-MB-231 cells treated with exosomes in the scratch assay showed similar results (39.86±3.47 in the experimental group vs. 24.48±2.97 in the control group, P<0.05). Conclusion: TAM-derived exosomes can be ingested and endocytosed by MDA-MB-231 cells, and promote their migration and invasion in vitro. [ABSTRACT FROM AUTHOR]

Purpose: Anti-angiogenic agents have shown promise for treating advanced hepatocellular carcinoma (HCC), and the primary mechanism of low-dose metronomic chemotherapy using traditional cytotoxic drugs is anti-angiogenic. This study evaluated the efficacy of metronomic capecitabine and thalidomide after cool-tip radiofrequency ablation (RFA), relative to RFA alone, for treating patients with HCC.Methods and materials: Patients with HCC were randomly apportioned to a test group (n = 22) receiving metronomic chemotherapy with capecitabine and thalidomide after RFA, or a control group (n = 28) receiving RFA only. Serum circulating endothelial cells (CECs) and vascular endothelial growth factor (VEGF) were measured in all patients before and 1 month after RFA treatment. Enhanced computed tomography or ultrasound imaging was performed to evaluate efficacy during 12 months of follow-up. The treatment groups were further stratified as HCC within or outside the Milan criteria for transplantation.Results: One month post-treatment, the tumour response rate (TRR), including complete response and partial response rate, of the test and control groups was statistically similar. At 12 months, the TRR of the test group (68.2%) was significantly higher than that of the control group (35.7%). In the test group, the TRR of patients whose tumour burdens were outside the Milan criteria was significantly higher than that of the control group. One month post-treatment, CECs and VEGF levels of the test group were significantly lower than baseline, while those of the control group were significantly higher. At the end of the 12-month follow-up, there was a progression-free survival (PFS) benefit of 2 months in the test group.Conclusion: Metronomic capecitabine and thalidomide after RFA significantly reduced recurrence of HCC and extended PFS, especially for HCC outside the Milan criteria, perhaps via reduction of serum CECs and VEGF levels and inhibition of tumour angiogenesis. [ABSTRACT FROM PUBLISHER]