BackgroundHigh frequency of recurrence is the major cause of the poor outcomes for patients with hepatocellular carcinoma (HCC). microRNA (miR)-182-5p emerged as a high-priority miRNA in HCC and was found to be related to HCC metastasis. Whether the expression of miR-182-5p in tumor tissue correlated with early recurrence in HCC patients underwent curative surgery was unknown.MethodsReal-time PCR (RT-PCR) and in situ hybridization (ISH) were conducted to assess the expression of miR-182-5p in HCC cells and tissues. Cell Counting Kit-8 (CCK-8), transwell assays were performed to detected cells proliferation and migration ability. Flow cytometry assays were used to detect cell apoptosis rate, and xenograft model was employed to study miR-182-5p in HCC growth and lung metastasis. The target of miR-182-5p was validated with a dual-luciferase reporter assay and western blotting. Immunohistochemistry, immumoblotting, and immunoprecipitation were performed to test relative protein expression.ResultsWe showed that high expression of miR-182-5p in tumor tissues correlated with poor prognosis as well as early recurrence in HCC patients underwent curative surgery. miR-182-5p enhanced motility and invasive ability of HCC cells both in vitro and in vivo. miR-182-5p directly targets 3′-UTR of FOXO3a and repressed FOXO3a expression, activating AKT/FOXO3a pathway to promote HCC proliferation. Notably, miR-182-5p activated Wnt/β-catenin signaling by inhibiting the degradation of β-catenin and enhancing the interaction between β-catenin and TCF4 which was mediated by repressed FOXO3a.ConclusionsConsistently, miR-182-5p can be a potential predictor of early recurrence for HCC patients underwent curative surgery, and FOXO3a plays a key mediator in miR-182-5p induced HCC progression.
Colony-stimulating factor-1 (CSF-1) and its receptor, CSF-1R, regulate the differentiation and function of macrophages and play an important role in macrophage infiltration in the context of hepatocellular carcinoma (HCC). The therapeutic effects of CSF-1R blockade in HCC remain unclear. In this study, we found that CSF-1R blockade by PLX3397, a competitive inhibitor with high specificity for CSF-1R tyrosine kinase, significantly delayed tumor growth in mouse models. PLX3397 inhibited the proliferation of macrophages in vitro, but intratumoral macrophage infiltration was not decreased by PLX3397 in vivo. Gene expression profiling of tumor-associated macrophages (TAMs) showed that TAMs from the PLX3397-treated tumors were polarized toward an M1-like phenotype compared with those from vehicle-treated tumors. In addition, PLX3397 treatment increased CD8 + T-cell infiltration, whereas CD4 + T-cell infiltration was decreased. Further study revealed that tumor cell-derived CSF-2 protected TAMs from being depleted by PLX3397. In conclusion, CSF-1R blockade delayed tumor growth by shifting the polarization rather than the depletion of TAMs. CSF-1R blockade warrants further investigation in the treatment of HCC.on May 9, 2018.
BackgroundOur previous study reported that microRNA-26a (miR-26a) inhibited tumor progression by inhibiting tumor angiogenesis and intratumoral macrophage infiltration in hepatocellular carcinoma (HCC). The direct roles of miR-26a on tumor cell invasion remain poorly understood. In this study, we aim to explore the mechanism of miR-26a in modulating epithelial-mesenchymal transition (EMT) in HCC.MethodsIn vitro cell morphology and cell migration were compared between the hepatoma cell lines HCCLM3 and HepG2, which were established in the previous study. Overexpression and down-regulation of miR-26a were induced in these cell lines, and Western blot and immunofluorescence assays were used to detect the expression of EMT markers. Xenograft nude mouse models were used to observe tumor growth and pulmonary metastasis. Immunohistochemical assays were conducted to study the relationships between miR-26a expression and enhancer of zeste homolog 2 (EZH2) and E-cadherin expression in human HCC samples.ResultsDown-regulation of miR-26a in HCCLM3 and HepG2 cells resulted in an EMT-like cell morphology and high motility in vitro and increased in tumor growth and pulmonary metastasis in vivo. Through down-regulation of EZH2 expression and up-regulation of E-cadherin expression, miR-26a inhibited the EMT process in vitro and in vivo. Luciferase reporter assay showed that miR-26a directly interacted with EZH2 messenger RNA (mRNA). Furthermore, the expression of miR-26a was positively correlated with E-cadherin expression and inversely correlated with EZH2 expression in human HCC tissue.ConclusionsmiR-26a inhibited the EMT process in HCC by down-regulating EZH2 expression.
Polyunsaturated free fatty acids (PUFAs) are known to play critical roles for the development, maintenance, and function of the brain. Recently, we reported that G-protein coupled receptor 40 (GPR40), one type of PUFA receptors, is expressed throughout the adult primate central nervous system including the hippocampus. This opens a possibility that PUFA might act as extracellular signaling molecules at the GPR40 receptor to regulate neuronal function. Here we studied protein expression of GPR40 in the neurogenic niche of the adult monkey hippocampus under normal and postischemic conditions. Confocal laser microscope analysis of immunostained sections revealed GPR40 immunoreactivity in neural progenitors, immature neurons, astrocytes and endothelial cells of the subgranular zone (SGZ) of the dentate gyrus (DG); a well-known neurogenic niche within the adult brain. Immunoblotting analysis showed that the GPR40 protein increased significantly in the second week after global cerebral ischemia as compared with the control. This was compatible with the postischemic increment of GPR40-positive cells in the SGZ as detected by immunofluorescence imaging. Taken together with our previous findings of the SGZ progenitor cell upregulation after ischemia, the present data suggest that PUFA such as docosahexaenoic acid may act via GPR40 to regulate adult hippocampal neurogenesis in primates.
Gorham-Stout disease (GSD) is an exceedingly rare disease characterized by progressive osteolysis and angiomatosis. We investigate the features of this disease and evaluate the effects of bisphosphonates (BPs) on it. The clinical, radiological, and pathological characteristics of 12 patients diagnosed with GSD were summarized. Immunohistochemical staining with specific lymphatic endothelial markers (D2-40), vascular markers (CD 31, CD 34), and vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor 3 (VEGFR-3) was performed in specimens of bone biopsy. Patients were treated with either BPs or conjunction therapy of radiation and BPs. The effects of BPs were evaluated by the change of radiological progression, bone mineral density (BMD) and bone turnover biomarkers. To further evaluate the prognosis, a literature review was done. Idiopathic massive osteolysis was found in all patients, including 11 polyostotic and one mono-ostotic osteolysis. Soft tissue lymphangioma was presented in four patents. Four patients were complicated with chylothorax. Endothelial cells lining the proliferative vessels were positive for CD31 and CD34 and D2-40. Mild expression of VEGF and VEGFR-3 was also revealed. Stabilization in osteolysis and improvement in BMD were observed after single therapy with BPs or combined with radiotherapy. High mortality rate was found in patients with chylothorax. Spontaneous, progressive osteolysis is the most typical sign of GSD. BPs and radiotherapy can contribute to the clinical stabilization in bone lesion of GSD. The complicated chylothorax possibly indicates poor prognosis.
BackgroundmicroRNAs (miRNAs) have been reported to modulate macrophage colony-stimulating factor (M-CSF) and macrophages. The aim of this study was to find whether miR-26a can suppress M-CSF expression and the recruitment of macrophages.MethodsHepatocellular carcinoma (HCC) cell lines with decreased or increased expression of miR-26a were established in a previous study. M-CSF expression by tumor cells was measured by enzyme-linked immunosorbent assay, and cell migration assays were used to explore the effect of HCC cell lines on macrophage recruitment in vitro. Real-time PCR measured a panel of mRNAs expressed by macrophages. Xenograft models were used to observe tumor growth. Immunohistochemistry was conducted to study the relation between miR-26a expression and M-CSF expression and macrophage recruitment in patients with HCC.ResultsEctopic expression of miR-26a reduced expression of M-CSF. The conditioned medium (CM) from HepG2 cells that overexpressed miR-26a reduced the migration ability of THP-1 cells stimulated by phorbol myristate acetate (PMA) increased expression of interleukin (IL)-12b or IL-23 mRNA and decreased expression of chemokine (C-C motif) ligand (CCL)22, CCL17, and IL-10 mRNA, in comparison to the medium from the parental HepG2 cells. These effects could be interrupted by the PI3K/Akt pathway inhibitor LY294002. Ectopic expression of miR-26a in HCC cells suppressed tumor growth, M-CSF expression, and infiltration of macrophages in tumors. Similar results were also found when using HCCLM3 cells. Furthermore, the expression of miR-26a was inversely correlated with M-CSF expression and macrophage infiltration in tumor tissues from patients with HCC.ConclusionsmiR-26a expression reduced M-CSF expression and recruitment of macrophages in HCC.
We revealed the gene mutation spectrum in Chinese OI patients, and novel mutations identified here expanded the mutation catalog and genotype and phenotype relationships among OI patients.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
334 Leonard St
Brooklyn, NY 11211
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.