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Long non-coding RNAs (lncRNAs) regulate gene expression and play a significant role in cancer progression. Previously, downregulation of lncRNA MEG3 was shown to associate with poor clinical outcomes in melanoma patients. The basis for this association has not been described and the aims of this study were to identify a role for lncRNA MEG3 in melanoma and to describe its regulatory mechanism of action. RT-qPCR was used to detect lncRNA MEG3 expression in melanoma cells and tissues. Luciferase reporter assays were used to identify lncRNA MEG3 downstream targets. Melanoma cells were transfected with various expression vectors and these transfected cells were assessed for; migration, colony formation, proliferation, in vivo tumorigenesis, and metastatic potential. Melanoma cell lines were found to be sensitive to lncRNA MEG3 expression levels and overexpression was found to inhibit melanoma cell proliferation and invasion, both in vitro and in vivo. Luciferase reporter assays identified miR-208 and SOX4 as downstream targets of lncRNA MEG3. Overexpression of miR-208 and silencing of SOX4 rescued invasion and proliferation by cells that overexpressed lncRNA MEG3. Moreover, lncRNA MEG3 inhibited cancer stem cell differentiation and suppressed melanoma progression and metastasis through inhibition of miR-208 by SOX4.

The objective of this study was to evaluate the feasibility and clinical outcomes of S2-alar-iliac (S2AI) and iliac screw (IS) techniques in the lumbopelvic reconstruction of lumbosacral tuberculosis patients. From January 2014 to August 2016, 26 patients with lumbosacral tuberculosis attending the 8th Medical Centre of Chinese PLA General Hospital were included in this retrospective study. The subjects were divided into two groups based on the lumbopelvic fixation type (16 patients in the S2AI group, 10 patients in the IS group). The operation time, blood loss, length of hospitalisation, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, visual analogue scale (VAS), Oswestry Disability Index (ODI), ambulatory status, and 36-Item Short-Form Health Survey (SF-36) scores of the patients in two groups were recorded and compared. In addition, surgical complications were collected and analysed. The operation time and intraoperative blood loss were significantly lower in the S2AI group than that in the IS group (P .05). Compared with preoperative data, postoperative data showed significant improvement in ESR, CRP level, ODI scores, VAS scores, ambulatory status, and SF-36 (P .05), but there was no significant difference in remission degree between the two groups. Compared with IS group, The S2AI group had significantly lower rates of symptomatic screw prominence (P .05). Both the IS and S2AI fixation techniques can achieve satisfactory outcomes for the restoration of lumbosacral stability of lumbosacral tuberculosis. Furthermore, compared to the traditional IS fixation technique, the S2AI fixation technique can shorten operation time and reduce surgical trauma for the treatment of lumbosacral tuberculosis.

Macrophages (Mφs) are master regulators of the immune response and may serve as therapeutic targets in aging societies. This study aimed to determine the function of M1Mφ-exosomes (Exos) in the development of osteoporosis (OP) and the involvement of microRNA (miR)-98 and dual specificity phosphatase 1 (DUSP1). A murine model of OP was established using ovariectomies (OVX). Bone loss was observed in OVX-treated mice, which presented a reduced bone mineral density and number of bone trabecula, and it was further aggravated by treatment with M1Mφ-Exos. Exos also suppressed osteogenic differentiation of MC3T3-E1 cells. miRNA microarray analysis revealed that miR-98 levels were notably upregulated in cells after Exo treatment, and DUSP1 was confirmed as a target of miR-98. Meanwhile, downregulation of miR-98 or upregulation of DUSP1 restored the osteogenic differentiation ability of MC3T3-E1 cells. In addition, upregulation of DUSP1 reduced bone loss in murine bone tissues and suppressed JNK phosphorylation. In summary, M1Mφ-derived exosomal miR-98 exacerbates bone loss and OP by downregulating DUSP1 and activating the JNK signaling pathway. miR-98 may therefore serve as a therapeutic target in OP management. This article is protected by copyright. All rights reserved.

Although systemic therapies for melanoma have been improved, the 5-year survival rate of this aggressive cancer remains poor. It has been shown that hsa_circ_0062270 was upregulated in patients with melanoma. However, the relevant mechanism of hsa_circ_0062270 in the progression of melanoma remains unclear.The CCK-8, EdU staining, flow cytometry, and transwell assays were used to determine the viability, proliferation, apoptosis and invasion in melanoma cells. An in vivo animal study was performed finally.The level of hsa_circ_0062270 was significantly upregulated in melanoma cells. In addition, hsa_circ_0062270 knockdown markedly inhibited the viability, proliferation, invasion and promoted the apoptosis of melanoma cells. Cell division cycle protein 45 (CDC45) is the host gene of hsa_circ_0062270, and downregulation of hsa_circ_0062270 notably decreased the expression of CDC45 in melanoma cells. Rescue assays confirmed that hsa_circ_0062270 regulated the growth of melanoma cells through CDC45. Moreover, RIP analysis showed that hsa_circ_0062270 interacted with RNA-binding protein (RBP) EIF4A3. Furthermore, in vivo study indicated that knockdown of hsa_circ_0062270 inhibited the melanoma tumor growth in vivo.Downregulation of hsa_circ_0062270 can inhibit the progression of melanoma through downregulation of CDC45. Our findings provide biological mechanisms for the use of hsa_circ_0062270 as a biomarker for melanoma and potential therapeutic target.

Here we demonstrate a general approach to crafting a myriad of soluble octa-functionalized POSS derivatives by manipulating the sequential click reactions. After flexible modification with bio-functional groups, these uniform POSSs possess good biocompatibility, remarkable anticancer therapeutic effect and outstanding antibacterial activity in aqueous solutions. Notably, this ‘one-pot’ approach provides a simple strategy to produce customized POSS macromolecules, which may afford a novel platform for clear elucidation of more complex mechanisms and precise fabrication of high-performance biomaterials in various applications.

Circular RNAs (CircRNAs) have been found to be critical in tumorigenesis; however, the role of CircRNAs in osteosarcoma is to be further studied. In this study, we preliminarily identified the up-expressed CircRNAs and its downstream microRNA in osteosarcoma and investigated its potential regulation mechanism. Hsa_circ_0086996 (Circ_0086996) was found to upregulated in tumor tissue compared to adjacent tissue. Circ_0086996 was significantly overexpressed in osteosarcoma tissue, as well as in osteosarcoma cell lines of SAOS2 and MG-63. Circ_0086996 knockdown significantly suppressed cell proliferation, migration, and invasion. Circ_0086996 knockdown also induced cell cycle arrest in G0/G1 phaseand promoted cell apoptosis in SAOS2 and MG-63 cells. Bioinformatics analysis revealed that miR-125b-5p might be of complementary binding region with Circ_0086996, which was confirmed by dual-luciferase reporter assay. Moreover, Circ_0086996 could reverse the effect of miR-125b-5p, as knockdown of Circ_0086996 or application of miR-125b-5p both can inhibit cell proliferation, migration, invasion and promote cell apoptosis and cell cycle arrest. Our study discovers that Circ_0086996 acts as miR-125b-5p sponge to mediate the tumorigenicity, which could act as a potential biomarker for the osteosarcoma and provides a novel insight for the mechanism in osteosarcoma.

Melanoma is a common malignant tumor, which is associated with high mortality rate. The multiple-drug resistance of tumor cells often results in failure of chemotherapy. The aim of our study is to investigate the expression of Nav 1.6 in human melanoma cells and human epidermal melanocytes. Additionally, the effect of Na+channels on Ca+ current and mTOR activity in melanoma cells were also analyzed. The protein expression levels of Nav1.6 in human melanocyte PIG1, WM266 and WM115 cells were investigated by western blot. After treatment of Na+ channel inhibitor Tetroadotoxin (TTX) or mTOR inhibitor rapamycin (RAPA), the electrophysiological activity (Na+ current and Ca2+ current) in WM266 and WM115 cells was detected by patch clamp technique. The expression of mTORC1 phosphorylates S6 kinase (p-S6), cell invasion and migration, cell proliferation and cell apoptosis were also performed. Results shown that Nav 1.6 was overexpressed in WM266 and WM115 cells, and the inhibition of Na+ channel by TTX reduced Na+ current. Both TTX and RAPA suppressed Ca2+ current and the expression of p-S6, thus inducing Na+ channel which activates the mTOR-Ca2+ signaling pathway. Both TTX and RAPA suppressed cell invasion, migration and proliferation, and promoted cell apoptosis of WM266 cells. Thus, the Nav1.6 sodium channel promotes cell proliferation and invasion through mTOR-mediated Na+/Ca2+ exchange in melanoma. The observations will provide a new perspective for understanding the malignant biological behavior of melanoma cells, and potentially provide a new drug target.

The members of the integrin αv (ITGAV) family are widely expressed on many types of tumors and have been reported to be involved into angiogenesis, tumor metastases, and multicellular radioresistance. Osteosarcoma (OS) is the most common primary malignant bone tumor and the role of ITGAV in OS needs to be further elucidated. MicroRNAs are aberrantly expressed in a variety of cancers. Thus, the authors collected OS tissues (n = 15) and corresponding paracancerous tissues (n = 15) and found that the expression of miR-548c-3p was significantly downregulated in OS tissues and cell lines 143B, SaoS2, and HOS when compared to the corresponding paracancerous tissues and human osteoblast cell line hFOB (OB3), respectively. In addition, the authors identified that miR-548c-3p could directly target the 3'-untranslated region of ITGAV, and miR-548c-3p overexpression inhibits the mRNA and protein levels of ITGAV, which were confirmed by the luciferase reporter assays. Interestingly, they also uncovered that miR-548c-3p overexpression or knockdown of ITGAV remarkably suppressed cell vitality and promoted apoptosis and G2/M cell cycle arrest, leading to abrogating the ability of colony formation. The results indicated that the miR-548c-3p, similar to the target agents against integrin αv in clinical trials, could negatively regulate the ITGAV and be a promising tumor therapeutic target.

Symptomatic postoperative spinal epidural hematoma (SEH) and spontaneous spinal epidural hematoma (SSEH) are both rare conditions, and recurrent SEH occurs even less frequently. Therefore, we describe a case of symptomatic postoperative SEH after surgical evacuation of SSEH, which was diagnosed using magnetic resonance imaging (MRI) and managed with negative pressure wound therapy (NPWT). The authors classified the reported recurrent SEHs into two types based on the cause of their previous hematoma, which can be classified as spontaneous or postoperative. The characteristics, diagnosis, managements, and results of recurrent SEHs were analyzed. The authors suggest that the postoperative SEH in the Type II will be treated with NPWT, and the new classification will be helpful for prognosis, diagnosis, and management of the recurrent SEHs.

The present study aimed to determine the mechanisms of action of curcumin in osteosarcoma. Human osteosarcoma U-2 OS cells was purchased from the Cell Bank of the Chinese Academy of Sciences. RNA sequencing analysis was performed for 2 curcumin-treated samples and 2 control samples using Illumina deep sequencing technology. The differentially expressed genes were identified using Cufflink software. Enrichment and protein-protein interaction network analyses were performed separately using cluster Profiler package and Cytoscape software to identify key genes. Then, the mRNA levels of key genes were detected by quantitative reverse transcription polymerase chain reaction (RT-qPCR) in U-2 OS cells. Finally, cell apoptosis, proliferation, migration and invasion arrays were performed. In total, 201 DEGs were identified in the curcumin-treated group. EEF1A1 (degree=88), ATF7IP, HIF1A, SMAD7, CLTC, MCM10, ITPR1, ADAM15, WWP2 and ATP5C1, which were enriched in 'biological process', exhibited higher degrees than other genes in the PPI network. RT-qPCR demonstrated that treatment with curcumin was able to significantly increase the levels of CLTC and ITPR1 mRNA in curcumin-treated cells compared with control. In addition, targeting ITPR1 with curcumin significantly promoted apoptosis and suppressed proliferation, migration and invasion. Targeting ITPR1 via curcumin may serve an anticancer role by mediating apoptosis, proliferation, migration and invasion in U-2 OS cells.

Melanoma is a common malignant tumor, which is associated with high mortality rate. The multiple-drug resistance of tumor cells often results in failure of chemotherapy. The aim of our study is to investigate the expression of Nav 1.6 in human melanoma cells and human epidermal melanocytes. Additionally, the effect of Na+channels on Ca+ current and mTOR activity in melanoma cells were also analyzed. The protein expression levels of Nav1.6 in human melanocyte PIG1, WM266 and WM115 cells were investigated by western blot. After treatment of Na

It is widely accepted that mechanical injury to spinal cord can cause nervous system dysfunction, which leads to the loss of movement and sensation. However, the exact molecular mechanism is currently unclear. In this study, contused rat spinal cords were collected at 8 h, 1 day, 3, and 5 days after injury and the expression patterns of the proteins were monitored and quantified with two-dimensional gel electrophoresis-based proteomics. Fifty-one protein spots showed significant regulation at least at one time point. Of the 39 proteins, identified by mass spectrometry analysis and clustered into three down-regulation profiles and two up-regulation profiles, eight contusion-related proteins have been reported in previous proteomic studies of spinal cord whereas 31 proteins were described for the first time. For example, apoptosis-related protein of heat shock 70 kDa protein 1B increased after contusion, reaching the peak at 1 day; septin 7, a protein involved in cytoskeleton organization, maintained a steady increase for the first 5 days after injury; metabolism-related protein of 3-hydroxy-3-methylglutaryl-Coenzyme A synthase 1 was constantly down-regulated during the whole time course observed; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, epsilon polypeptide, associated with cell cycle progression, showed a gradual increase after contusion. To our knowledge, this is the first case of detailed and dynamic proteomic snapshots of contusion-induced spinal cord injury. Most of the identified proteins were found for the first time to be differentially expressed after spinal cord contusion, which may help explore the complex molecular cascades underlying the progressive pathologic changes in the contused spinal cord.

The spinal cord injury and regeneration-related gene #69 (SCIRR69), which was identified in our screen for genes upregulated after spinal cord injury, encode a protein belonging to the cAMP response element-binding protein (CREB)/ATF family of transcription factors. Our previous study showed that SCIRR69 functions as a transcriptional activator. However, the target gene regulated by SCIRR69 and its roles in injured neurons remain unknown. In this study, we showed that SCIRR69 is widely distributed in the central nervous system. Full-length SCIRR69 is an endoplasmic reticulum-bound protein. Following mechanical injury to neurons, SCIRR69 was induced and proteolytically cleaved by site-1 and site-2 proteases, and the proteolytically cleaved SCIRR69 (p60-SCIRR69) was translocated to the nucleus where it bound to brain-derived neurotrophic factor (BDNF) gene promoter II. In addition, loss- and gain-of-function studies confirmed that SCIRR69 is involved in the regulation of BDNF expression in injured neurons. As expected, the culture supernatants of PC12 cells stably expressing p60-SCIRR69 contained higher levels of BDNF, and more remarkably promoted neurite outgrowth in a spinal cord slice culture model in vitro than the supernatants of control cells. These results suggest that SCIRR69 is a novel regulator of the BDNF gene and may play an important role in the repair and/or regeneration of damaged neural tissues by specifically activating BDNF promoter II.