BackgroundOccurrence and progression of hepatocellular carcinoma (HCC) are associated with hepatitis B virus (HBV) infection. miR-1269b is up-regulated in HCC cells and tissues. However, the regulation of miR-1269b expression by HBV and the mechanism underlying the oncogenic activity of miR-1269b in HCC are unclear.MethodsReverse transcription quantitative PCR (RT-qPCR) was used to measure the expression of miR-1269b and target genes in HCC tissues and cell lines. Western blot analysis was used to assess the expression of miR-1269b target genes and related proteins. Using luciferase reporter assays and EMSA, we identified the factors regulating the transcriptional level of miR-1269b. Colony formation, flow cytometry and cell migration assays were performed to evaluate the phenotypic changes caused by miR-1269b and its target in HCC cells.ResultsWe demonstrated that the expression levels of pre-miR-1269b and miR-1269b in HBV-positive HepG2.2.15 cells were dramatically increased compared with HBV-negative HepG2 cells. HBx was shown to facilitate translocation of NF-κB from the cytoplasm to the nucleus, and NF-κB binds to the promoter of miR-1269b to enhance its transcription. miR-1269b targets and up-regulates CDC40, a cell division cycle 40 homolog. CDC40 increases cell cycle progression, cell proliferation and migration. Rescue experiment indicated that CDC40 promotes malignancy induced by miR-1269b in HCC cells.ConclusionWe found that HBx activates NF-κB to promote the expression of miR1269b, which augments CDC40 expression, contributing to malignancy in HCC. Our findings provide insights into the mechanisms underlying HBV-induced hepatocarcinogenesis.
Background: The relation between the expression of macrophage-colony stimulating factor-1 receptor (CSF-1R) and prognosis of cancer patients has been evaluated in multiple studies, but the results remain controversial. We, therefore, performed a meta-analysis and systematic review to figure out the role of CSF-1R in the prognosis of patients with cancer. Methods: Several databases were searched, including Web of Science, PubMed, and EMBASE. All human studies were published as full text. The Newcastle–Ottawa risk of bias scale was applied to evaluate the research. We extracted hazard ratios (HRs) with 95% confidence interval (95% CI) which assessed progression-free survival (PFS) and overall survival (OS) in order to assess the impacts of CSF-1R on the prognosis of cancer patients. Results: A total of 12 citations were identified, with studies including 2260 patients in different cancer types that met the eligibility criteria. It was suggested in a pooled analysis that the over-expression of CSF-1R was significantly related to worse PFS (HR: 1.68; P < .001, 1.25–2.10, 95% CI) and also poorer OS (HR=1.28; P < .001, 1.03–1.54, 95% CI). Analysis in subgroups indicated over-expressed CSF-1R was significantly associated with worse OS in hematological malignancy (HR = 2.29; P < .001, 1.49–3.09, 95% CI; model of fixed-effects; I 2 = 0.0%, P < .001). Sensitivity analysis suggested that there was no study influencing the stability of the results. Conclusions: The overexpression of CSF-1R was significantly predictive of worse prognosis in those who suffer from different kinds of malignancies, particularly in hematological malignancy, which indicates that it might be a potential biomarker of prognosis in cancer survival and a potential molecular target in the treatment of malignant tumors.
Purpose: To study the synergistic effect of a combination of granulocyte-macrophage colonystimulating factor and thymosin-α1 on the treatment of Lewis lung cancer transplanted tumor.Methods: C57BL/6 mice were used. A mouse model of Lewis lung cancer was established using Lewis lung cancer cell lines. The mice were randomly divided into blank control group, polyene taxol (DTX) group, DTX thymosin α1 (Tα-1) group, and DTX granulocyte-macrophage colony-stimulating factor (GM-CSF) group, with 8 mice per group. The degree of tumor inhibition, thymus mass, thymus index, spleen mass, spleen index, IL-6, TNF-1, IFN-1, CD4+, CD8+ T cells and the ratio of CD4+/CD8+ were determined by ELISA and flow cytometry.Results: Body mass, thymus mass, thymus index, spleen mass, spleen index, IL-6, TNF-1, IFN-1, CD4+, CD8+ T cells and the ratio of CD4+/CD8+ in DTX + Tα-1 group, DTX + GM-CSF group and DTX + Tα-1 + GM-CSF group were significantly elevated (p < 0.05), relative to the corresponding levels in DTXmice (p < 0.05). Body mass, degree of tumor inhibition, thymus mass, thymus index, spleen mass, spleen index, IL-6, TNF-1, IFN-1, CD4, CD8 T cells and CD4+/CD8+ ratio in DTX + Tα-1 + GM-CSF mice were significantly elevated, relative to the DTX + Tα-1 and DTX + GM-CSF groups (p < 0.05). Thestate of the tumor was significantly improved in the DTX + Tα-1 and DTX + GM-CSF mice.Conclusion: A combination treatment of GM-CSF, Tα-1 and DEX effectively enhances the resistance of mice and suppresses chemotherapy-induced decrease in body weight. This finding may be of clinical significance. Keywords: Granulocyte macrophage, Colony-stimulating factor, Thymosin, Docetaxel, Lewis lung cancer, Transplanted tumor
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