The SS18-SSX1 fusion gene has been shown to play important roles in the development of synovial sarcoma (SS), but the underlying molecular mechanisms and its downstream target genes are still not clear. Here SHC SH2-domain binding protein 1 (SHCBP1) was identified and validated to be a novel downstream target gene of SS18-SSX1 by using microarray assay, quantitative real-time (qPCR) and western blot. Expression of SHCBP1 was firstly confirmed in SS cell line and SS tissues. The effects of SHCBP1 overexpression or knockdown on SS cell proliferation and tumorigenicity were then studied by cell proliferation, DNA replication, colony formation, flow cytometric assays, and its in vivo tumorigenesis was determined in the nude mice. Meanwhile, the related signaling pathways of SHCBP1 were also examined in SS cells. The results indicated that SHCBP1 was significantly increased in SS cells and SS tissues compared with adjacent noncancerous tissues. The expression of SHCBP1 was demonstrated to be positively correlated with the SS18-SSX1 level. Overexpression and ablation of SHCBP1 promoted and inhibited, respectively, the proliferation and tumorigenicity of SS cells in vitro. SHCBP1 knockdown also significantly inhibited SS cell growth in nude mice, and lowered the MAPK/ERK and PI3K/AKT/mTOR signaling pathways and cyclin D1 expression. Our findings disclose that SHCBP1 is a novel downstream target gene of SS18-SSX1, and demonstrate that the oncogene SS18-SSX1 promotes tumorigenesis by increasing the expression of SHCBP1, which normally acts as a tumor promoting factor.
Feline leukemia virus subgroup C receptor 1 (FLVCR1) has been reported to have a crucial role in variety of biological processes, including cell proliferation, cell death, apoptosis, oxidative stress response, cellular differentiation and metabolism. However, little is known about its role in synovial sarcoma (SS). In the current study, FLVCR1 expression was analyzed in two SS cell lines (SW982 and HS-SY-II), and in eight SS tissues and paired adjacent non-tumor tissues using reverse transcription-quantitative polymerase chain reaction, western blot analysis and immunohistochemistry. Lentivirus-mediated short hairpin RNAs were used to knock down FLVCR1 expression in SW982 and HS-SY-II cells. The effects of FLVCR1 knockdown on the cell proliferation, clonogenicity, cell cycle and apoptosis in SS cells were evaluated by MTT, colony formation assay, flow cytometry analysis, western blotting and in vivo tumorigenesis in nude mice. In the current study, gene expression of FLVCR1 was upregulated in SS cell lines (SW982 and HS-SY-II) and SS tissues from patients. The protein levels of FLVCR1 in SS tissues were also significantly higher than in adjacent non-tumor tissues. Furthermore, suppressing the expression of FLVCR1 in SS cells using short hairpin RNA effectively attenuated cell proliferation, colony formation and impaired the cell cycle, and also significantly induced apoptosis and autophagy. In accordance with this, an in vivo tumorigenicity assay in mice demonstrated that suppression of FLVCR1 expression inhibited the growth of SS tumors implanted subcutaneously. Collectively, these results demonstrated that FLVCR1 may act as an oncoprotein, and have key roles in promoting proliferation and tumorigenicity of SS, and this may shed new light on finding novel therapeutic strategies against SS.
The present examination includes manufacture and portrayal of cryogel bio-composite implants containing chitosan-gelatin (CS-GT), cerium–zinc doped hydroxyapatite (CS-GT/Ce-Zn-HA) by cryogelation technique. The prepared cryogel biocomposites (CS-GT/HA and CS-GT/Ce-Zn-HA) were described by scanning electron microscope (SEM) and X-Ray diffraction (XRD) contemplates. The expansion of Ce-Zn in the CS-GT implants essentially expanded growing, diminished swelling, expanded protein sorption, and expanded bactericidal movement. The CS-GT/Ce-Zn-HA biocomposite had non-toxic towards rodent osteoblast cells. So the created CS-GT/Ce-Zn-HA biocomposite has favorable and potential applications over the CS-GT/HA platforms for bone tissue engineering.
Previous studies have suggested that impairment secondary to mechanical injury is a major cause of irreversible damage to the spinal cord. Inflammatory chemokines have been shown to play an important role in the pathological and physiological consequences of secondary spinal cord injury (SCI). The aim of the present study was to evaluate how changes in the expression levels of the cellular chemokine, monocyte chemoattractant peptide-1 (MCP-1), and the chemotaxis of inflammatory cells (monocytes and macrophages) are involved in the process of SCI. RNA interference methods were used to study the mechanisms that protect residual neurons after SCI in an attempt to explore novel, early interventions for managing SCI. Our results suggested that inhibiting inflammation alleviates nerve cell injury caused by apoptosis and provides a potentially important approach for the future treatment of secondary SCI.
A new type of tissue-engineered bone was constructed by seeding hVEGF165 gene-modified endothelial progenitor cells into the nanohydroxyapatite/collagen/poly(L-lactic acid) scaffolds. These were implanted into the segmental femoral defects of rats to explore the promotion of angiogenesis and osteogenesis. The bone marrow of Sprague Dawley rats was cultured and proliferated, and the endothelial progenitor cells were transfected with Ad5–hVEGF165–EGFP. The gene-modified endothelial progenitor cells were seeded into the nanohydroxyapatite/collagen/poly(L-lactic acid) scaffolds; the growth was observed by scanning electron microscope, and the proliferation was evaluated by methyl thiazolyl tetrazolium assay. In vivo, 80 Sprague Dawley rats were divided randomly into four groups; segmental femoral defects (5 mm) were made and allografted: group A with hVEGF165/endothelial progenitor cells–nanohydroxyapatite/collagen/poly(L-lactic acid), group B with mock endothelial progenitor cells–nanohydroxyapatite/collagen/poly(L-lactic acid), group C with endothelial progenitor cells–nanohydroxyapatite/collagen/poly(L-lactic acid), and group D with scaffolds only. Radiographic, histological, and microvessel density tests were performed to evaluate the angiogenic and osteogenic ability. Reverse transcription polymerase chain reaction and western blot results showed that the target gene was expressed by endothelial progenitor cells. The scanning electron microscope findings and methyl thiazolyl tetrazolium assay revealed that endothelial progenitor cells were attached and proliferated within the nanohydroxyapatite/collagen/poly(L-lactic acid) scaffolds. The average radiographic score and capillary density were the highest in group A, and those in groups B and C were higher than that of group D. The histology showed osteogenesis and scaffold degradation in group A, with less in groups B and C and little in group D. The hVEGF165 gene-modified endothelial progenitor cells, which promoted angiogenesis and osteogenesis in bone-defected areas and the hVEGF165/endothelial progenitor cells–nanohydroxyapatite/collagen/poly(L-lactic acid) composites, may have potential application in repair of segmental bone defects.
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