Epithelial TIPE1 Protein Guards against Colitis by Inhibiting TNF-α-Mediated Inflammation.

Intestinal epithelial cells (IECs) at the internal/external interface orchestrate the mucosal immune response, and IEC dysfunction has been linked to multiple inflammatory diseases, including inflammatory bowel disease. In this study, we found that a member of the TNF-α-induced protein 8 (TNFAIP8 or TIPE) family called TIPE1 is indispensable for maintaining epithelial cell barrier integrity and homeostasis under inflammatory conditions. TIPE1-deficient mice, or chimeric mice that were deficient in TIPE1 in their nonhematopoietic cells, were more sensitive to dextran sulfate sodium-induced experimental colitis; however, TIPE1 deficiency had no impact on the development of inflammation-associated and sporadic colorectal cancers. Mechanistically, TIPE1 prevented experimental colitis through modulation of TNF-α-dependent inflammatory response in IECs. Importantly, genetic deletion of both TIPE1 and its related protein TNFAIP8 in mice led to the development of spontaneous chronic colitis, indicating that both of these two TIPE family members play crucial roles in maintaining intestinal homeostasis. Collectively, our findings highlight an important mechanism by which TIPE family proteins maintain intestinal homeostasis and prevent inflammatory disorders in the gut.

Design of a Double-Photoelectrode Sensing System with a Metal-Organic Framework-Based Antenna-like Strategy for Highly Sensitive Detection of PD-L1.

Currently, the construction of heterojunctions as a method to enhance photoelectrochemical (PEC) activity has shown prospective applications in the analytical field. Restricted by carrier separation at the interface, developing a heterojunction sensing platform with high sensitivity remains challenging. Here, a double-photoelectrode PEC sensing platform was fabricated based on an antenna-like strategy by integrating MIL-68(In)-NH2, a p-type metal-organic framework (MOF) photocatalyst, as a photocathode with the type-II heterojunction of CdSe/MgIn2S4 as a photoanode synchronously. According to the ligand-to-metal charge transition (LMCT), the photo-generated carriers of MIL-68(In)-NH2 transferred from the organic ligand to the metal cluster, which provides an efficient antenna-like transfer path for the charge at the heterojunction interface. In addition, the sufficient Fermi energy difference between the double photoelectrode provides the continuous internal driving force required for rapid carrier separation at the anode detection interface, significantly improving the photoelectric conversion efficiency. Hence, compared with the traditional heterojunction single electrode, the photocurrent response of the double-photoelectrode PEC sensing platform developed using the antenna-like strategy is 2.5 times stronger. Based on this strategy, we constructed a PEC biosensor for the detection of programed death-ligand 1 (PD-L1). The elaborated PD-L1 biosensor exhibited sensitive and precise detection capability with a detection range of 1 × 10-5 to 1 × 103 ng/mL and a lower detection limit of 3.26 × 10-6 ng/mL and demonstrated the feasibility of serum sample detection, providing a novel and viable approach for the unmet clinical need of PD-L1 quantification. More importantly, the charge separation mechanism at the heterojunction interface proposed in this study provides new creative inspiration for designing sensors with high-sensitivity PEC performance.

Water Activation Triggered by Cu-Co Double-Atom Catalyst for Silane Oxidation.

High-performance catalysts sufficient to significantly reduce the energy barrier of water activation are crucial in facilitating reactions that are restricted by water dissociation. Herein we present a Cu-Co double-atom catalyst (CuCo-DAC), which possesses a uniform and well-defined CuCoN6 (OH) structure, and works together to promote water activation in silane oxidation. The catalyst achieves superior catalytic performance far exceeding that of single-atom catalysts (SACs). Various functional silanes are converted into silanols with up to 98 % yield and 99 % selectivity. Kinetic studies show that the activation energy of silane oxidation by CuCo-DAC is significantly lower than that of Cu single-atom catalyst (Cu-SAC) and Co single-atom catalyst (Co-SAC). Theoretical calculations demonstrate two different reaction pathways where water splitting is the rate-determining step and it is accelerated by CuCo-DAC, whereas H2 formation is key for its single-atom counterpart.

TIPE1-mediated autophagy suppression promotes nasopharyngeal carcinoma cell proliferation via the AMPK/mTOR signalling pathway.

Recent studies have shown that tumour necrosis factor-α-induced protein 8 like-1(TIPE1) plays distinct roles in different cancers. TIPE1 inhibits tumour proliferation and metastasis in a variety of tumours but acts as an oncogene in cervical cancer. The role of TIPE1 in nasopharyngeal carcinoma (NPC) remains unknown. Interestingly, TIPE1 expression was remarkably increased in NPC tissue samples compared to adjacent normal nasopharyngeal epithelial tissue samples in our study. TIPE1 expression was positively correlated with that of the proliferation marker Ki67 and negatively correlated with patient lifespan. In vitro, TIPE1 inhibited autophagy and induced cell proliferation in TIPE1-overexpressing CNE-1 and CNE-2Z cells. In addition, knocking down TIPE1 expression promoted autophagy and decreased proliferation, whereas overexpressing TIPE1 increased the levels of pmTOR, pS6 and P62 and decreased the level of pAMPK and the LC3B. Furthermore, the decrease in autophagy was remarkably rescued in TIPE1-overexpressing CNE-1 and CNE-2Z cells treated with the AMPK activator AICAR. In addition, TIPE1 promoted tumour growth in BALB/c nude mice. Taken together, results indicate that TIPE1 promotes NPC progression by inhibiting autophagy and inducing cell proliferation via the AMPK/mTOR signalling pathway. Thus, TIPE1 could potentially be used as a valuable diagnostic and prognostic biomarker for NPC.

Circular RNA circFOXO3 promotes prostate cancer progression through sponging miR-29a-3p.

Circular RNA FOXO3 (CircFOXO3, also termed as Hsa_circ_0006404) is derived from exon 2 of forkhead box O3 (FOXO3) gene, and abnormal expression is shown in different diseases. However, whether circFOXO3 plays important roles in tumorigenesis and progression of prostate cancer (PCa) remains unclear. In this study, we found that circFOXO3 was up-regulated in both PCa tissues and serum samples. Moreover, circFOXO3 was positively correlated with the Gleason score in PCa samples. CircFOXO3 was observed to be up-regulated in Gleason score > 6 PCa samples compared with Gleason score = 6 PCa samples. Knock-down circFOXO3 could remarkably inhibit PCa cell cycle, proliferation and promote cell apoptosis in vitro. Furthermore, we demonstrated circFOXO3 could act as miR-29a-3p sponge to up-regulate SLC25A15 expression by bioinformatics analysis, dual-luciferase reporter assays and biotinylated RNA pull-down assays. SLC25A15 could reverse the tumour suppressing roles of knock-down circFOXO3 in PCa. Of note, we found that miR-29a-3p was down-regulated; however, SLC25A15 was overexpressed in PCa samples compared with normal tissues. In conclusion, circFOXO3 acts as a miR-29a-3p sponge to exhibit oncogenic activity that affects the cell cycle and cell apoptosis in PCa through transcriptional up-regulation of SLC25A15. Our analysis suggests circFOXO3 could act as promising prostate cancer biomarkers.

A novel nonsense variant in PLS3 causes X-linked osteoporosis in a Chinese family.

Osteoporosis is a complex bone metabolic disorder. Genetic factors play an important role in the development of osteoporosis. Mutations in more than 15 genes have been identified to be responsible for osteoporosis to date. Most recently, the gene PLS3 encoding plastin 3 was recognized to be involved in X-linked osteoporosis. Here, we recruited a four-generation Chinese family with X-linked osteoporosis, which had its onset in childhood and was characterized by peripheral fractures and low bone mineral density. All affected individuals shared a nonsense variant (c.244C > T) in exon 4 of PLS3 on Xq23. The variant in affected individuals segregated with the osteoporosis phenotype. By restriction analysis using Dra I, this variant was confirmed in all affected individuals but was not detected in unaffected family members or in 100 unrelated Chinese male controls. The variant was predicted to cause a premature termination of messenger RNA (mRNA) translation (p.Gln82*). The mutant mRNA degraded via the mechanism of "nonsense-mediated mRNA decay." In the present study, we identified a novel nonsense variant of PLS3 in early-onset X-linked osteoporosis and provided a novel insight into the molecular mechanism underlying the pathogenesis of osteoporosis.

Hepatitis B core protein promotes liver cancer metastasis through miR-382-5p/DLC-1 axis.

The hepatitis B virus core protein (HBc), also named core antigen, is well-known for its key role in viral capsid formation and virus replication. Recently, studies showed that HBc has the potential to control cell biology activity by regulating host gene expression. Here, we utilized miRNA microarray to identify 24 upregulated miRNAs and 21 downregulated miRNAs in HBc-expressed HCC cells, which were involved in multiple biological processes, including cell motility. Consistently, the in vitro transwell assay and the in vivo tail-vein injection model showed HBc promotion on HCC metastasis. Further, the miRNA-target gene network analysis displayed that the deleted in liver cancer (DLC-1) gene, an important negative regulator for cell motility, was potentially targeted by several differentially expressed miRNAs in HBc-introduced cells. Introduction of miRNAs mimics or inhibitors and 3'UTR luciferase activity assay proved that miR-382-5p efficiently suppressed DLC-1 expression and its 3'-UTR luciferase reporter activity. Importantly, cotransfection of miR-382-5p mimics/inhibitors and the DLC-1 expression vector almost abrogated HBc promotion on cell motility, indicating that the miR-382-5p/DLC-1 axis is important for mediating HBc-enhanced HCC motility. Clinical HCC samples also showed a negative correlation between miR-382-5p and DLC-1 expression level. Furthermore, HBc-positive HCC tissues showed high miR-382-5p level and reduced DLC-1 expression. In conclusion, our findings revealed that HBc promoted HCC motility by regulating the miR-382-5p/DLC-1 axis, which might provide a novel target for clinical diagnosis and treatment.

TIPE1 promotes cervical cancer progression by repression of p53 acetylation and is associated with poor cervical cancer outcome.

Previous studies have shown that TIPE1 inhibits tumor proliferation and metastasis in certain cancers; however, increased expression of TIPE1 is observed in cervical cancer cell lines and tissues, indicating it might exert a distinctive role in cervical cancer. Cell and xenograft tumorigenicity assays showed that TIPE1 facilitates cervical cancer progression in this study. Further investigation demonstrated that TIPE1 binds to p53 and impairs its activity via inhibition of its acetylation. In addition, TIPE1 promoted cell proliferation and suppressed cisplatin susceptibility in a p53-dependent manner, indicating that TIPE1 facilitates cervical cancer progression primarily through the p53 pathway. TIPE1 expression in clinical samples also demonstrated that its upregulation predicts poor prognosis in patients with cervical cancer. Taken together, the results of this study showed that TIPE1 serves as an oncogene by restricting p53 activity in the development of cervical cancer, suggesting that TIPE1 will provide a new potential target for cervical cancer therapy and can be used as a biomarker to predict patient prognosis.

OMS-2-Supported Cu Hydroxide-Catalyzed Benzoxazoles Synthesis from Catechols and Amines via Domino Oxidation Process at Room Temperature.

In the presence of manganese oxide octahedral molecular sieve (OMS-2) supported copper hydroxide Cu(OH)x/OMS-2, aerobic synthesis of benzoxazoles from catechols and amines via domino oxidation/cyclization at room temperature is achieved. This heterogeneous benzoxazoles synthesis initiated by the efficient oxidation of catechols over Cu(OH)x/OMS-2 tolerates a variety of substrates, especially amines containing sensitive groups (hydroxyl, cyano, amino, vinyl, ethynyl, ester, and even acetyl groups) and heterocycles, which affords functionalized benzoxazoles in good to excellent yields by employing low catalyst loading (2 mol % Cu). The characterization and plausible catalytic mechanism of Cu(OH)x/OMS-2 are described. The notable features of our catalytic protocol such as the use of air as the benign oxidant and EtOH as the solvent, mild conditions, ease of product separation, being scalable up to the gram level, and superior reusability of catalyst (up to 10 cycles) make it more practical and environmentally friendly for organic synthesis.

Role of citrullination modification catalyzed by peptidylarginine deiminase 4 in gene transcriptional regulation.

Peptidylarginine deiminase 4 (PADI4), a new histone modification enzyme, which converts both arginine and monomethyl-arginine to citrulline, has gained massive attention in recent years as a potential regulator of gene transcription. Recent studies have shown that arginine residues R2, R8, R17, and R26 in the H3 tail and R3 in the H4 tail can be deiminated by PADI4. This kind of histone post-translational modification has the potential to antagonize histone methylation and coordinate with histone deacetylation to regulate gene transcription. PADI4 also deiminates non-histone proteins, such as p300, NPM1, ING4, RPS2, and DNMT3A. PADI4 has been shown to involve in cell apoptosis and differentiation. Moreover, PADI4 can interact with tumor suppressor p53 and regulate the transcriptional activity of p53. Dysregulation of PADI4 is implicated in a variety of diseases, including rheumatoid arthritis, tumor development, and multiple sclerosis. A wide variety of PADI4 inhibitors have been identified. Further understanding of PADI4 functions may lead to novel diagnostic and therapeutic approaches in these diseases. This review summarizes the recent progress in the study of the regulation mechanism of PADI4 on gene transcription and the major physiological functions of PADI4 in human diseases.

Tim-4 protects mice against lipopolysaccharide-induced endotoxic shock by suppressing the NF-κB signaling pathway.

Endotoxic shock is the primary cause of morbidity and mortality in hospital patients, creating an urgent need to explore the mechanisms involved in sepsis. Our previous studies showed that T-cell immunoglobulin- and mucin-domain-containing molecule-4 (Tim-4) attenuated the inflammatory response through regulating the functions of macrophages. However, the mechanism by which Tim-4 does this has not been fully elucidated. In this study, we found that Tim-4 expression was increased in lipopolysaccharide (LPS)-induced endotoxic shock. Interestingly, the survival rate of mice in the Tim-4 overexpression group was higher than that of the control group after LPS administration. To investigate the function of Tim-4 in LPS-induced inflammation, we further demonstrated that Tim-4 attenuated LPS-induced endotoxic shock by inhibiting cytokine production by macrophages. Blocking expression of Tim-4 and nuclear factor-kappa B (NF-κB) signal inhibition showed that Tim-4 inhibited cytokine production via NF-κB signaling pathway. This study indicates that Tim-4 may exert its immune modulation by regulating inflammatory factor secretion and might act as a novel potential target for inflammatory diseases, especially endotoxic shock.

Association between rs6812193 polymorphism and sporadic Parkinson's disease susceptibility.

Recently, the association of a single nucleotide polymorphism rs6812193 C/T with sporadic Parkinson's disease (PD) susceptibility has been widely evaluated, but the results remained inconsistent. This association should be clarified because of the importance of it on human health and quality of life. We performed a comprehensive meta-analysis to evaluate the association between the rs6812193 polymorphism and sporadic PD. PubMed was used to retrieve articles published up to June 2014 for all studies evaluating the rs6812193 polymorphism and PD in humans. Ethnicity-specific subgroup analysis was also performed based on ethnicity susceptibility. A total of 17 independent study samples (15 Caucasians and 2 Asians) including 17,956 cases and 52,751 controls were used in the presented study. The MAFT (minor allele T frequency) in PD patients of European descent is obviously higher than Asian cases (p < 0.01). The results suggested the rs6812193 polymorphism (allele T vs. C) is significantly associated with PD susceptibility among overall samples (OR 0.882, 95 % CI 0.856-0.908) and Caucasian population (OR 0.881, 95 % CI 0.856-0.907), but not in Asian samples (OR 0.918, 95 % CI 0.721-1.168). No evidence of publication bias was observed. Throughout our analysis, the rs6812193 polymorphism is significantly associated with sporadic PD susceptibility in Caucasian samples, and ethnicity might be the key point of inconsistency in rs6812193 studies. Further studies are warranted to re-examine the observed associations, especially in different ethnicities.

Characterization of solid and liquid carbonization products of polyvinyl chloride (PVC) and investigation of the PVC-derived adsorbent for the removal of organic compounds from water.

The transformation of plastic wastes into value-added carbon materials is a promising strategy for the recycling of plastics. Commonly used polyvinyl chloride (PVC) plastics are converted into microporous carbonaceous materials using KOH as an activator via simultaneous carbonization and activation for the first time. The optimized spongy microporous carbon material has a surface area of 2093 m2 g-1 and a total pore volume of 1.12 cm3 g-1, and aliphatic hydrocarbons and alcohols are yielded as the carbonization by-products. The PVC-derived carbon materials exhibit outstanding adsorption performance for removing tetracycline from water, and the maximum adsorption capacity reaches 1480 mg g-1. The kinetic and isotherm patterns for tetracycline adsorption follow the pseudo-second-order and Freundlich models, respectively. Adsorption mechanism investigation indicates that pore filling and hydrogen bond interaction are mainly responsible for the adsorption. This study provides a facile and environmentally friendly approach for valorizing PVC into adsorbents for wastewater treatment.

A novel natural killer cell-related signatures to predict prognosis and chemotherapy response of pancreatic cancer patients.

Background: Natural killer (NK) cells are involved in monitoring and eliminating cancers. The purpose of this study was to develop a NK cell-related genes (NKGs) in pancreatic cancer (PC) and establish a novel prognostic signature for PC patients. Methods: Omic data were downloaded from The Cancer Genome Atlas Program (TCGA), Gene Expression Omnibus (GEO), International Cancer Genome Consortium (ICGC), and used to generate NKG-based molecular subtypes and construct a prognostic signature of PC. NKGs were downloaded from the ImmPort database. The differences in prognosis, immunotherapy response, and drug sensitivity among subtypes were compared. 12 programmed cell death (PCD) patterns were acquired from previous study. A decision tree and nomogram model were constructed for the prognostic prediction of PC. Results: Thirty-two prognostic NKGs were identified in PC patients, and were used to generate three clusters with distinct characteristics. PCD patterns were more likely to occur at C1 or C3. Four prognostic DEGs, including MET, EMP1, MYEOV, and NGFR, were found among the clusters and applied to construct a risk signature in TCGA dataset, which was successfully validated in PACA-CA and GSE57495 cohorts. The four gene expressions were negatively correlated with methylation level. PC patients were divided into high and low risk groups, which exerts significantly different prognosis, clinicopathological features, immune infiltration, immunotherapy response and drug sensitivity. Age, N stage, and the risk signature were identified as independent factors of PC prognosis. Low group was more easily to happened on PCD. A decision tree and nomogram model were successfully built for the prognosis prediction of PC patients. ROC curves and DCA curves demonstrated the favorable and robust predictive capability of the nomogram model. Conclusion: We characterized NKGs-derived molecular subtypes of PC patients, and established favorable prognostic models for the prediction of PC prognosis, which may serve as a potential tool for prognosis prediction and making personalized treatment in PC.

TIPE2 sensitizes breast cancer cells to paclitaxel by suppressing drug-induced autophagy and cancer stem cell properties.

Drug resistance is a great obstacle to the clinical application of paclitaxel (PTX) in breast cancer treatment. Chemoresistance can be either primary or acquired. Multifarious factors are related to drug resistance. Among these factors, drug-induced autophagy has been shown to contribute to acquired chemoresistance in cancer cells. Additionally, cancer stem cells (CSCs) drive primary chemoresistance. Recent advances regarding TIPE2 demonstrate that TIPE2 enhances osteosarcoma and non-small cell lung cancer cell sensitivity to cisplatin. However, the role of TIPE2 in PTX resistance in breast cancer cells has not been elucidated. Here, the in vitro and in vivo study demonstrated that TIPE2 sensitized breast cancer cells to PTX by suppressing drug-induced autophagy and CSC properties. Mechanistically, we found that TIPE2 activated the AKT/mTOR signalling pathway and inhibited the TAK1/MAPK signalling pathway to suppress drug-induced autophagy. Moreover, TIPE2 inhibited TAK1/NF-κB activation to reduce breast CSC properties. Collectively, our results first elucidated the inhibitory role of TIPE2 in breast cancer chemoresistance. Thus, TIPE2 may be a new target for breast cancer chemotherapy.

Ketogenic diet protects MPTP-induced mouse model of Parkinson's disease via altering gut microbiota and metabolites.

The ketogenic diet (KD) is a low-carbohydrate, high-fat regime that is protective against neurodegenerative diseases. However, the impact of KD on Parkinson's disease (PD) and its mechanisms remains unclear. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD was fed with KD for 8 weeks. Motor function and dopaminergic neurons were evaluated. Inflammation in the brain, plasma, and colon tissue were also measured. Fecal samples were assessed by 16S rDNA gene sequencing and untargeted metabolomics. We found that KD protected motor dysfunction, dopaminergic neuron loss, and inflammation in an MPTP mouse model of PD. 16S rDNA sequencing revealed that MPTP administration significantly increased Citrobacter, Desulfovibrio, and Ruminococcus, and decreased Dubosiella, whereas KD treatment reversed the dysbiosis. Meanwhile, KD regulated the MPTP-induced histamine, N-acetylputrescine, d-aspartic acid, and other metabolites. Fecal microbiota transplantation using feces from the KD-treated mice attenuated the motor function impairment and dopaminergic neuron loss in antibiotic-pretreated PD mice. Our current study demonstrates that KD played a neuroprotective role in the MPTP mouse model of PD through the diet-gut microbiota-brain axis, which may involve inflammation in the brain and colon. However, future research is warranted to explore the explicit anti-inflammatory mechanisms of the gut-brain axis in PD models fed with KD.

Brønsted-acid sites promoted degradation of phthalate esters over MnO2: Mineralization enhancement and aquatic toxicity assessment.

Advanced oxidation processes (AOPs) are important technologies for aqueous organics removal. Despite organic pollutants can be degraded via AOPs generally, high mineralization of them is hard to achieve. Herein, we synthesized a manganese oxide nanomaterial (H2-OMS-2) with abundant Brønsted-acid sites via ion-exchange of cryptomelane-type MnO2 (OMS-2), and tested its catalytic performance for the degradation of phthalate esters via peroxymonosulfate (PMS) activation. About 99% of dimethyl phthalate (DMP) at a concentration of 20 mg/L could be degraded within 90 min and 82% of it could be mineralized within 180 min over 0.6 g/L of catalyst and 1.8 g/L of PMS. The catalyst could activate PMS to generate SO4-˙ and ·OH as the dominant reactive oxygen species to reach complete degradation of DMP. Especially, the higher TOC removal rate was obtained due to the rich Brønsted-acid sites and surface oxygen vacancies on the catalyst. Kinetics and mechanism study showed that MnII/MnIII might work as the active sites during the catalytic process with a lower reaction energy barrier of 55.61 kJ/mol. Furthermore, the catalyst could be reused for many times through the regeneration of the catalytic ability. The degradation and TOC removal efficiencies were still above 98% and 65% after seven consecutive cycles, respectively. Finally, H2-OMS-2-catalyzed AOPs significantly reduced the organismal developmental toxicity of the DMP wastewater through the investigation of zebrafish model system. The present work, for the first time, provides an idea for promoting the oxidative degradation and mineralization efficiencies of aqueous organic pollutants by surface acid-modification on the catalysts.

Tumor Necrosis Factor-α-Induced Protein 8-Like 2 Fosters Tumor-Associated Microbiota to Promote the Development of Colorectal Cancer.

Although increasing evidence links the gut microbiota with the development of colorectal cancer, the molecular mechanisms for microbiota regulation of tumorigenesis are not fully understood. Here, we found that a member of the TNFα-induced protein 8 (TNFAIP8) family called TIPE2 (TNFAIP8-like 2) was significantly upregulated in murine intestinal tumors and in human colorectal cancer, and colorectal cancer with high expression of Tipe2 mRNA associated with reduced survival time of patients. Consistent with these findings, TIPE2 deficiency significantly inhibited the development of colorectal cancer in mice treated with azoxymethane/dextran sodium sulfate and in Apcmin/+ mice. TIPE2 deficiency attenuated the severity of colitis by successfully resolving and restricting colonic inflammation and protected colonic myeloid cells from death during colitis. Transplantation of TIPE2-deficient bone marrow into wild-type mice successfully dampened the latter's tumorigenic phenotype, indicating a hematopoietic-specific role for TIPE2. Mechanistically, restricting the expansion of Enterobacteriaceae/Escherichia coli (E. coli) decreased intestinal inflammation and reduced the incidence of colonic tumors. Collectively, these data suggest that hematopoietic TIPE2 regulates intestinal antitumor immunity by regulation of gut microbiota. TIPE2 may represent a new therapeutic target for treating colorectal cancer.

TIPE1 inhibits osteosarcoma tumorigenesis and progression by regulating PRMT1 mediated STAT3 arginine methylation.

Osteosarcoma (OS), the most common primary malignancy of the bone, has a poor prognosis due to its high mortality rate and high potential for metastasis. Thus, it is urgently necessary to explore functional molecular targets of therapeutic strategies for osteosarcoma. Here, we reported that TIPE1 expression was decreased in osteosarcoma tissues compared to normal and adjacent nontumor tissues, and its expression was negatively related to tumor stage and tumor size. Functional assays showed that TIPE1 inhibited osteosarcoma carcinogenesis and metastatic potential both in vivo and in vitro. Furthermore, we investigated that the STAT3 signaling pathway was significantly downregulated after TIPE1 overexpression. Mechanistically, TIPE1 bind to the catalytic domain of PRMT1, which deposits an asymmetric dimethylarginine (ADMA) mark on histone/non-histone proteins, and thus inhibited PRMT1 mediated STAT3 methylation at arginine (R) residue 688. This abolished modification decreased STAT3 transactivation and expression, by which subsequently suppressed osteosarcoma malignancy. Taken together, these data showed that TIPE1 inhibits the malignant transformation of osteosarcoma through PRMT1-mediated STAT3 arginine methylation and ultimately decreases the development and metastasis of osteosarcoma. TIPE1 might be a potential molecular therapeutic target and an early biomarker for osteosarcoma diagnosis.