RILP inhibits tumor progression in osteosarcoma via Grb10-mediated inhibition of the PI3K/AKT/mTOR pathway.

BACKGROUND: Rab-interacting lysosomal protein (RILP) contains an alpha-helical coil with an unexplored biological function in osteosarcoma. This study investigated the expression of RILP in osteosarcoma cells and tissues to determine the effect of RILP on the biological behaviors of osteosarcoma cells and the underlying mechanism. METHODS: Tumor Immune Estimation Resource (TIMER) database, The Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) database were used for bioinformatic analysis. Co-immunoprecipitation experiment was used to determine whether the two proteins were interacting. In functional tests, cell counting kit-8 (CCK-8) assay, colony formation assay, wound healing assay, transwell invasion assay, Immunofluorescence (IF) assay and immunohistochemical (IHC) assay were performed. RESULTS: Overexpression of RILP significantly inhibited proliferation and impaired metastasis ability of osteosarcoma cells, while silencing of RILP showed the opposite trend. RNA-seq data analysis was applied in 143B cells and pathway enrichment analysis revealed that differentially expressed genes were mainly enriched in the PI3K/AKT pathway. We further verified that overexpression of RILP restrained the PI3K/AKT/mTOR signaling pathway and induced autophagy in osteosarcoma cells, while the opposite trend was observed when PI3K pathway activator 740Y-P was used. 3-Methyladenine (3-MA), a selective autophagy inhibitor, partially attenuated the inhibitory effect of RILP on the migration and invasion ability of osteosarcoma cells, suggesting the involvement of autophagy in epithelial-mesenchymal transition regulation in osteosarcoma cells. Growth factor receptor binding protein-10 (Grb10), an adaptor protein, was confirmed as a potential target of RILP to restrain the PI3K/AKT signaling pathway. We subcutaneously injected stably overexpressing 143B osteosarcoma cells into nude mice and observed that overexpression of RILP inhibited tumor growth by inhibiting the PI3K/AKT/mTOR pathway. CONCLUSION: Our study revealed that the expression of RILP was associated with favorable prognosis of osteosarcoma and RILP inhibits proliferation, migration, and invasion and promotes autophagy in osteosarcoma cells via Grb10-mediated inhibition of the PI3K/AKT/mTOR signaling pathway. In the future, targeting RILP may be a potential strategy for osteosarcoma treatment.

Non-line-of-sight reconstruction via structure sparsity regularization.

Non-line-of-sight (NLOS) imaging allows for the imaging of objects around a corner, which enables potential applications in various fields, such as autonomous driving, robotic vision, medical imaging, security monitoring, etc. However, the quality of reconstruction is challenged by low signal-to-noise ratio (SNR) measurements. In this study, we present a regularization method, referred to as structure sparsity (SS) regularization, for denoising in NLOS reconstruction. By exploiting the prior knowledge of structure sparseness, we incorporate nuclear norm penalization into the cost function of the directional light-cone transform (DLCT) model for the NLOS imaging system. This incorporation effectively integrates the neighborhood information associated with the directional albedo, thereby facilitating the denoising process. Subsequently, the reconstruction is achieved by optimizing a directional albedo model with SS regularization using the fast iterative shrinkage-thresholding algorithm (FISTA). Notably, the robust reconstruction of occluded objects is observed. Through comprehensive evaluations conducted on both synthetic and experimental datasets, we demonstrate that the proposed approach yields high-quality reconstructions, surpassing the state-of-the-art reconstruction algorithms, especially in scenarios involving short exposure and low-SNR measurements.

Construction of a prognostic risk score model based on the ARHGAP family to predict the survival of osteosarcoma.

BACKGROUND: Osteosarcoma (OS) is the most common primary malignancy of bone tumors. More and more ARHGAP family genes have been confirmed are to the occurrence, development, and invasion of tumors. However, its significance in osteosarcoma remains unclear. In this study, we aimed to identify the relationship between ARHGAP family genes and prognosis in patients with OS. METHODS: OS samples were retrieved from the TCGA and GEO databases. We then performed LASSO regression analysis and multivariate COX regression analysis to select ARHGAP family genes to construct a risk prognosis model. We then validated this prognostic model. We utilized ESTIMATE and CIBERSORT algorithms to calculate the stroma and immune scores of samples, as well as the proportions of tumor infiltrating immune cells (TICs). Finally, we conducted in vivo and in vitro experiments to investigate the effect of ARHGAP28 on osteosarcoma. RESULTS: We selected five genes to construct a risk prognosis model. Patients were divided into high- and low-risk groups and the survival time of the high-risk group was lower than that of the low-risk group. The high-risk group in the prognosis model constructed had relatively poor immune function. GSEA and ssGSEA showed that the low-risk group had abundant immune pathway infiltration. The overexpression of ARHGAP28 can inhibit the proliferation, migration, and invasion of osteosarcoma cells and tumor growth in mice, and IHC showed that overexpression of ARHGAP28 could inhibit the proliferation of tumor cells. CONCLUSION: We constructed a risk prognostic model based on five ARHGAP family genes, which can predict the overall survival of patients with osteosarcoma, to better assist us in clinical decision-making and individualized treatment.

A Series of New Pyrrole Alkaloids with ALR2 Inhibitory Activities from the Sponge Stylissa massa.

Twelve new and four known alkaloids including five different structural scaffolds were isolated from the sponge Stylissa massa collected in the South China Sea. Compound 1 is the first identified precursor metabolite of the classic 5/7/5 tricyclic skeleton with unesterified guanidine and carboxyl groups, compounds 2-5 and 13-15 belong to the spongiacidin-type pyrrole imidazole alkaloids (PIAs). Z- and E-configurations of the spongiacidin-type PIAs often appeared concomitantly and were distinguished by the chemical shift analysis of 13C NMR spectra. The structures of all twelve new compounds were determined by NMR, MS, and ECD analysis combined with single-crystal data of compounds 1, 5, and 10. In the aldose reductase (ALR2) inhibitory assay, six 5/7/5 tricyclic compounds (2-5, 13-15) displayed significant activities. Compounds 13 and 14, as the representative members of spongiacidin-PIAs, demonstrated their ALR2-targeted activities in SPR experiments with KD values of 12.5 and 6.9 µM, respectively.

Focus shaping of high numerical aperture lens using physics-assisted artificial neural networks.

We present a physics-assisted artificial neural network (PhyANN) scheme to efficiently achieve focus shaping of high numerical aperture lens using a diffractive optical element (DOE) divided into a series of annular regions with fixed widths. Unlike the conventional ANN, the PhyANN does not require the training using labeled data, and instead output the transmission coefficients of each annular region of the DOE by fitting weights of networks to minimize the delicately designed loss function in term of focus profiles. Several focus shapes including sub-diffraction spot, flattop spot, optical needle, and multi-focus region are successfully obtained. For instance, we achieve an optical needle with 10λ depth of focus, 0.41λ lateral resolution beyond diffraction limit and high flatness of almost the same intensity distribution. Compared to typical particle swarm optimization algorithm, the PhyANN has an advantage in DOE design that generates three-dimensional focus profile. Further, the hyperparameters of the proposed PhyANN scheme are also discussed. It is expected that the obtained results benefit various applications including super-resolution imaging, optical trapping, optical lithography and so on.

Glucocorticoid Enhanced the Expression of Ski in Osteonecrosis of Femoral Head: The Effect on Adipogenesis of Rabbit BMSCs.

Glucocorticoid (GC)-induced osteonecrosis has been considered as the most serious side effect in long-term or over-dose steroid therapy. The decreased bone mass and increased marrow fat tissue demonstrated that GC can destroy the normal differentiation of bone marrow mesenchymal stem cells (BMSCs), which accelerates adipogenesis but not osteogenesis. However, the underlying mechanisms are still unclear. Ski, an evolutionary conserved protein, is a multifunctional transcriptional regulator that involved in regulating signaling pathways associated with adipogenesis differentiation, but the concrete function remains unclear. In this work, we first established a methylprednisolone (MPS)-induced osteonecrosis of femoral head (ONFH) rabbit model, in which the expression of Ski, PPAR-γ, and FABP4 was up-regulated compared with control group, and then we induced the isolated BMSCs from rabbit with dexamethasone (Dex) in vitro and the results showed that the Ski expression was up-regulated by Dex in a dose- and time-dependent manner. Therefore, we demonstrated that the expression of Ski was up-regulated in glucocorticoid-related osteonecrosis disease in vivo and in vitro. Moreover, the adipogenesis differentiation capacity of BMSCs was enhanced after induced by Dex, which was identified by Oil Red O staining, and the up-regulated PPAR-γ and FABP4 expression. To further study the function of Ski in BMSC after induced by Dex, Ski specific small interfering RNA (Ski-siRNA) was used. Results showed that knockdown of Ski obviously decreased adipogenesis differentiation evident by Oil Red O staining, and the expression of PPAR-γ and FABP4 was down-regulated simultaneously. Collectively, our findings suggest that Ski increased significantly during glucocorticoid-induced adipogenic differentiation of BMSCs, and the expression level was consistent with adipogenic-related proteins including PPAR-γ and FABP4. Based on the above data, we believe that Ski might become a new molecule in the treatment of GC-induced ONFH and our study could provide a basis for further study on the detailed function of Ski in ONFH.

CRM197-Coupled Der p 2 Peptides Suppress Allergic Airway Inflammation in a Der p 2-Induced Asthma Mouse Model.

Allergic diseases affect more than 25% of the global population. Der p 2 is the major allergen of the house dust mite (HDM) Dermatophagoides pteronyssinus. Allergen-specific immunotherapy is the only treatment to change the course of allergic diseases. In this study, two synthesized Der p 2 peptides coupled to cross-reacting material 197 (CRM197) showed reduced IgE reactivity and allergenic activity. CRM197-coupled Der p 2 peptides induced rDer p 2-specific IgG1 antibodies in mice, which could inhibit HDM-allergic patients' IgE binding to rDer p 2. The immunity effects of CRM197-coupled Der p 2 peptides were studied in an rDer p 2-induced asthma mouse model. CRM197-coupled Der p 2 peptides can suppress asthmatic airway inflammation in this model. Analysis of IL-4, IL-5, and IFN-γ levels in bronchoalveolar lavage fluid revealed that the suppression was associated with a shift from a Th2 to a Th1 response. Thus, CRM197-bound Der p 2 peptides exhibited less allergenic activity than the rDer p 2 allergen, which preserved immunogenicity and may be candidates for mite allergy vaccines.

Noninterleaved Metasurface for (26-1) Spin- and Wavelength-Encoded Holograms.

Nanostructured metasurfaces demonstrate extraordinary capabilities to control light at the subwavelength scale, emerging as key optical components to physical realization of multitasked devices. Progress in multitasked metasurfaces has been witnessed in making a single metasurface multitasked by mainly resorting to extra spatial freedom, for example, interleaved subarrays, different angles. However, it imposes a challenge of suppressing the cross-talk among multiwavelength without the help of extra spatial freedom. Here, we introduce an entirely novel strategy of multitasked metasurfaces with noninterleaved single-size Si nanobrick arrays and minimalist spatial freedom demonstrating massive information on 6-bit encoded color holograms. The interference between electric dipole and magnetic dipole in individual Si nanobricks with in-plane orientation enables manipulating six bases of incident photons simultaneously to reconstructed 6-bit wavelength- and spin-dependent multicolor images. Those massively reconstructed images can be distinguished by pattern recognition. It opens an alternative route for integrated optics, data encoding, security encryption, and information engineering.

Frequency subspace amplitude flow for phase retrieval.

A novel approach, termed frequency subspace amplitude flow (FSAF), is proposed to reconstruct complex-valued signal from "phaseless" measurements. The proposed FSAF consists of two stages: the first stage approximates low-frequency coefficients of an unknown signal by the spectral method, and the second stage refines the results by the truncated conjugate gradient of amplitude-based nonconvex formulation. FSAF is easy to implement and applicable to natural images, where no additional constraint is needed. Extensive experiments with 1D signals, 2D images, and natural images corroborate significant improvements by using the proposed FSAF method over the state of the art. Especially for sample complexity, FSAF pushes the state of the art for exactly reconstructing complex natural signals (with a size of n) from 3.2n to 2.2n under the Gaussian model, and from 5n to 3n under the coherent diffraction pattern (CDP) model without increasing computational complexity. More importantly, the proposed method is highly flexible and can be easily adapted to the existing algorithms under different noise models.

Conjugate gradient method for phase retrieval based on the Wirtinger derivative.

A conjugate gradient Wirtinger flow (CG-WF) algorithm for phase retrieval is proposed in this paper. It is shown that, compared with recently reported Wirtinger flow and its modified methods, the proposed CG-WF algorithm is able to dramatically accelerate the convergence rate while keeping the dominant computational cost of each iteration unchanged. We numerically illustrate the effectiveness of our method in recovering 1D Gaussian signals and 2D natural color images under both Gaussian and coded diffraction pattern models.

High-level expression and purification of the major house dust mite allergen Der p 2 in Escherichia coli.

Der p 2, a major allergen derived from the house dust mite Dermatophagoides pteronyssinus, is one of the most clinically relevant allergens worldwide. Recombinant Der p 2 (rDer p 2) is useful in clinical diagnosis and disease-specific immunotherapy. However, previous studies showed that Der p 2 can only be expressed in Escherichia coli (E. coli) cells as inclusion bodies, thus protein refolding is required to obtain functional products. Here we report a new method to produce biologically active Der p 2 protein in E. coli. N-terminal hexahistidine- and trigger factor (TF)-tagged Der p 2 was expressed in soluble form in E. coli and purified using a combination of chromatography processes. This procedure produced milligram-level high purity Der p 2 per liter of bacterial culture. Moreover, far-UV region circular dichroism (CD) analysis and serum specific IgE reactivity test demonstrated that the secondary structure and IgE reactivity properties of rDer p 2 produced in our study were almost identical to those of natural Der p 2 (nDer p 2). In conclusion, the method developed in this work provides a useful tool for the production of immunologically active recombinant Der p 2 for clinical applications.

Detection of Two Drug-Resistance Mutants of the Cytomegalovirus by High-Resolution Melting Analysis.

BACKGROUND: Human cytomegalovirus (CMV) is an opportunistic pathogen that can be treated with ganciclovir. Mutations in the UL97 gene of CMV render the virus ganciclovir resistance. These include H520Q and C603W mutations, against which we developed a novel genotyping assay for their identification. METHODS: PCR reactions were performed to amplify fragments of the UL97 gene containing H520Q or C603W mutations. High resolution melting analysis (HRMA) coupled with unlabeled DNA probes was employed to identify the shift in melting temperature of the probe-template complex, which reflexes the presence of point mutations. RESULTS: Melting point analysis performed on the dimeric DNA of PCR products of UL97 gene could not identify mutations in the gene. When coupled to unlabeled probes, point mutations in UL97 can be identified by analyzing the melting curve of probe-template complex. When WT and mutant UL97 DNAs were mixed together to mimic heterogeneous viral population in clinical samples, the genotyping assay is sensitive enough to detect H520Q and C603W mutants that constitute 10% of total DNA input. CONCLUSION: Probe-based HRMA is effective in detecting H520Q and C603W mutations in the UL97 gene of CMV.

Structural insights into the Cdt1-mediated MCM2-7 chromatin loading.

Initiation of DNA replication in eukaryotes is exquisitely regulated to ensure that DNA replication occurs exactly once in each cell division. A conserved and essential step for the initiation of eukaryotic DNA replication is the loading of the mini-chromosome maintenance 2-7 (MCM2-7) helicase onto chromatin at replication origins by Cdt1. To elucidate the molecular mechanism of this event, we determined the structure of the human Cdt1-Mcm6 binding domains, the Cdt1(410-440)/MCM6(708-821) complex by NMR. Our structural and site-directed mutagenesis studies showed that charge complementarity is a key determinant for the specific interaction between Cdt1 and Mcm2-7. When this interaction was interrupted by alanine substitutions of the conserved interacting residues, the corresponding yeast Cdt1 and Mcm6 mutants were defective in DNA replication and the chromatin loading of Mcm2, resulting in cell death. Having shown that Cdt1 and Mcm6 interact through their C-termini, and knowing that Cdt1 is tethered to Orc6 during the loading of MCM2-7, our results suggest that the MCM2-7 hexamer is loaded with its C terminal end facing the ORC complex. These results provide a structural basis for the Cdt1-mediated MCM2-7 chromatin loading.

Exploring the Osteogenic Potential of Zinc-Doped Magnesium Phosphate Cement (ZMPC): A Novel Material for Orthopedic Bone Defect Repair.

In orthopedics, the repair of bone defects remains challenging. In previous research reports, magnesium phosphate cements (MPCs) were widely used because of their excellent mechanical properties, which have been widely used in the field of orthopedic medicine. We built a new k-struvite (MPC) cement obtained from zinc oxide (ZnO) and assessed its osteogenic properties. Zinc-doped magnesium phosphate cement (ZMPC) is a novel material with good biocompatibility and degradability. This article summarizes the preparation method, physicochemical properties, and biological properties of ZMPC through research on this material. The results show that ZMPC has the same strength and toughness (25.3 ± 1.73 MPa to 20.18 ± 2.11 MPa), that meet the requirements of bone repair. Furthermore, the material can gradually degrade (12.27% ± 1.11% in 28 days) and promote osteogenic differentiation (relative protein expression level increased 2-3 times) of rat bone marrow mesenchymal stem cells (rBMSCs) in vitro. In addition, in vivo confirmation revealed increased bone regeneration in a rat calvarial defect model compared with MPC alone. Therefore, ZMPC has broad application prospects and is expected to be an important repair material in the field of orthopedic medicine.

A Bioactive Gelatin-Methacrylate Incorporating Magnesium Phosphate Cement for Bone Regeneration.

Maintaining proper mechanical strength and tissue volume is important for bone growth at the site of a bone defect. In this study, potassium magnesium phosphate hexahydrate (KMgPO4·6H2O, MPC) was applied to gelma-methacrylate hydrogel (GelMA) to prepare GelMA/MPC composites (GMPCs). Among these, 5 GMPC showed the best performance in vivo and in vitro. These combinations significantly enhanced the mechanical strength of GelMA and regulated the degradation and absorption rate of MPC. Considerably better mechanical properties were noted in 5 GMPC compared with other concentrations. Better bioactivity and osteogenic ability were also found in 5 GMPC. Magnesium ions (Mg2+) are bioactive and proven to promote bone tissue regeneration, in which the enhancement efficiency is closely related to Mg2+ concentrations. These findings indicated that GMPCs that can release Mg2+ are effective in the treatment of bone defects and hold promise for future in vivo applications.

ZNF692 promotes osteosarcoma cell proliferation, migration, and invasion through TNK2-mediated activation of the MEK/ERK pathway.

BACKGROUND: Osteosarcoma is a diverse and aggressive bone tumor. Driver genes regulating osteosarcoma initiation and progression remains incompletely defined. Zinc finger protein 692 (ZNF692), a kind of Krüppel C2H2 zinc finger transcription factor, exhibited abnormal expression in different types of malignancies and showed a correlation with the clinical prognosis of patients as well as the aggressive characteristics of cancer cells. Nevertheless, its specific role in osteosarcoma is still not well understood. METHODS: We investigated the dysregulation and clinical significance of ZNF692 in osteosarcoma through bioinformatic method and experimental validation. A range of in vitro assays, including CCK-8, colony formation, EdU incorporation, wound healing, and transwell invasion tests, were conducted to assess the impact of ZNF692 on cell proliferation, migration, and invasion in osteosarcoma. A xenograft mouse model was established to evaluate the effect of ZNF692 on tumor growth in vivo. Western blot assay was used to measure the protein levels of MEK1/2, P-MEK1/2, ERK1/2, and P-ERK1/2 in cells that had been genetically modified to either reduce or increase the expression of ZNF692. The relationship between ZNF692 and tyrosine kinase non-receptor 2 (TNK2) were validated by qRT-PCR, chromatin immunoprecipitation and luciferase reporter assays. RESULTS: Expression of ZNF692 was increased in both human osteosarcoma tissues and cell lines. Furthermore, the expression of ZNF692 served as an independent predictive biomarker in osteosarcoma. The results of the survival analysis indicated that increased expression of ZNF692 was associated with worse outcome. Downregulation of ZNF692 inhibits the proliferation, migration, and invasion of osteosarcoma cells, whereas upregulation of ZNF692 has the opposite impact. Western blot assay indicates that reducing ZNF692 decreases phosphorylation of MEK1/2 and ERK1/2, whereas increasing ZNF692 expression enhances their phosphorylation. U0126, a potent inhibitor specifically targeting the MEK/ERK signaling pathway, partially counteracts the impact of ZNF692 overexpression on the proliferation, migration, and invasion of osteosarcoma cells. In addition, ZNF692 specifically interacts with the promoter region of TNK2 and stimulates the transcription of TNK2 in osteosarcoma cells. Forcing the expression of TNK2 weakens the inhibitory impact of ZNF692 knockdown on P-MEK1/2 and P-ERK1/2. Similarly, partly inhibiting TNK2 counteracts the enhancing impact of ZNF692 overexpression on the phosphorylation of MEK1/2 and ERK1/2. Functional tests demonstrate that the suppressive effects of ZNF692 knockdown on cell proliferation, migration, and invasion are greatly reduced when TNK2 is overexpressed. In contrast, the reduction of TNK2 hinders the ability of ZNF692 overexpression to enhance cell proliferation, migration, and invasion. CONCLUSION: ZNF692 promotes the proliferation, migration, and invasion of osteosarcoma cells via the TNK2-dependent stimulation of the MEK/ERK signaling pathway. The ZNF692-TNK2 axis might potentially function as a possible predictive biomarker and a promising target for novel therapeutics in osteosarcoma.

Isoquercitrin restrains the proliferation and promotes apoptosis of human osteosarcoma cells by inhibiting the Wnt/ß-catenin pathway.

Currently, chemotherapeutic drugs are widely used for the treatment of osteosarcoma. However, many of these drugs exhibit shortcomings such as poor efficacy, high toxicity, and tolerance. Isoquercitrin (ISO) is a traditional Chinese medicine that has been proved to exert good therapeutic effects on various tumors; however, its role in osteosarcoma has not been reported. Here, we observed that ISO exerted a marked inhibitory effect on the occurrence and development of osteosarcoma in a time- and dose-dependent manner. First, we determined that ISO significantly inhibited proliferation, induced EMT-related migration and invasion and induced apoptosis of osteosarcoma cells in vitro. Concurrently, we also observed that both ß-catenin and its downstream genes (c-Myc, CyclinD1, and Survivin) were significantly down-regulated. To verify if the anti-tumor effect of ISO was related to the Wnt/ß-catenin signaling pathway, we altered the protein expression level of ß-catenin using recombinant lentivirus, then we observed that the effects of ISO on the proliferation, metastasis, and apoptosis of osteosarcoma cells were significantly reversed. Additionally, we used a nude mouse xenograft model and observed that ISO significantly inhibited the growth of osteosarcoma and improved the survival rate of the animal models. In conclusion, this study demonstrates that ISO can exert anti-tumor effects in part by inhibiting the Wnt/ß-catenin signaling pathway, thus providing a new potential therapeutic strategy for the treatment of osteosarcoma.

Zyxin Inhibits the Proliferation, Migration, and Invasion of Osteosarcoma via Rap1-Mediated Inhibition of the MEK/ERK Signaling Pathway.

Zyxin (ZYX) is an actin-interacting protein with unknown biological functions in patients with osteosarcoma. This research sought to understand how ZYX affects the biological behavior of osteosarcoma cells and to identify the associated mechanism. Firstly, ZYX expression was decreased in osteosarcoma, and its higher expression indicated better outcomes in patients with osteosarcoma. ZYX overexpression significantly inhibited the proliferation, migration, and invasion of osteosarcoma cells, whereas ZYX silencing resulted in the opposite trend. Subsequently, we found that the Rap1 signaling pathway was significantly correlated with ZYX expression as reported in The Cancer Genome Atlas's database using bioinformatic analysis. Moreover, we found that ZYX overexpression regulated the Rap1/MEK/ERK axis, and osteosarcoma cell growth, migration, and invasion were consequently restrained. Additionally, by administering tumor cells subcutaneously to nude mice, a mouse model of transplanted tumors was created. Compared to the control group, the ZYX overexpression group's tumors were lighter and smaller, and the ZYX/Rap1 axis was activated in the ZYX overexpression group. Taken together, our results suggest that ZYX inhibits osteosarcoma cell proliferation, migration, and invasion by regulating the Rap1/MEK/ERK signaling pathway. ZYX might be crucial in the clinical management of osteosarcoma and is a promising novel therapeutic target in patients with this disease.

TRIM26 inhibited osteosarcoma progression through destabilizing RACK1 and thus inactivation of MEK/ERK signaling.

Osteosarcoma is a highly aggressive malignant tumor that is common in the pediatric population and has a high rate of disability and mortality. Recent studies have suggested that the tripartite motif-containing family genes (TRIMs) play critical roles in oncogenesis in several cancers. TRIM26, one of the TRIMs family genes, was more frequently reported to exert a tumor-suppressive role, while its detailed functional roles in the osteosarcoma progression were still unknown and require further investigation. Herein, we found that TRIM26 was markedly downregulated in osteosarcoma tissues and cells. Survival analysis revealed that higher expression of TRIM26 was associated with better prognosis and its expression was an independent protective factor in osteosarcoma. Functional analysis demonstrated that overexpression of TRIM26 inhibited osteosarcoma cell proliferation and invasion via inhibiting the EMT process and MEK/ERK signaling. In contrast, the silence of TRIM26 caused the opposite effect. RACK1, a member of the Trp-Asp repeat protein family, was identified as a novel target of TRIM26. TRIM26 could interact with RACK1 and accelerate the degradation of RACK1, thus inactivation of MEK/ERK signaling. Overexpression of RACK1 could attenuate the inhibitory effect of TRIM26 overexpression on p-MEK1/2 and p-ERK1/2, and silence of RACK1 could partly impair the effect of TRIM26 knockdown-induced upregulation of p-MEK1/2 and p-ERK1/2. Further, a series of gain- and loss-of-function experiments showed that decreased malignant behaviors including cell proliferation and invasion in TRIM26-upregulated cells were reversed when RACK1 was overexpressed, whereas RACK1 knockdown diminished the increased malignant phenotypes in TRIM26-silenced osteosarcoma cells. In conclusion, our study indicated that TRIM26 inhibited osteosarcoma progression via promoting proteasomal degradation of RACK1, thereby resulting in inactivation of MEK/ERK signaling, and impeding the EMT process.

Retraction: Enhanced bone defect repairing effects in glucocorticoid-induced osteonecrosis of the femoral head using a porous nano-lithium-hydroxyapatite/gelatin microsphere/erythropoietin composite scaffold.

Retraction of 'Enhanced bone defect repairing effects in glucocorticoid-induced osteonecrosis of the femoral head using a porous nano-lithium-hydroxyapatite/gelatin microsphere/erythropoietin composite scaffold' by Donghai Li et al., Biomater. Sci., 2018, 6, 519-537, https://doi.org/10.1039/C7BM00975E.