Dehydroabietylamine exerts antitumor effects by affecting nucleotide metabolism in gastric cancer.

Nucleotide metabolism is the ultimate and most critical link in the self-replication process of tumors, including gastric cancer (GC). However, in clinical treatment, classic anti-tumor drugs such as 5-fluorouracil (5-FU) are mostly metabolic analogues of purines or pyrimidines, which lack specificity for tumor cells and therefore have significant side effects. It is unclear whether there are other drugs that can target nucleotide metabolism, except for nucleic acid analogues. Here, we found that a natural compound, dehydroabietylamine (DHAA), significantly reduced the viability and proliferation of GC cells and organoids. DHAA disrupts purine and pyrimidine metabolism of GC cells, causing DNA damage and further inducing apoptosis. DHAA treatment decreased transcription and protein levels of key enzymes involved in nucleotide metabolism pathway, with significant reductions in the expression of pyrimidine metabolism key enzymes CAD, DHODH, and purine metabolism key enzymes PAICS. We also found that DHAA directly binds to and reduces the expression of Forkhead box K2 (FOXK2), a common transcription factor for these metabolic enzymes. Ultimately, DHAA was shown to delay tumorigenesis in K19-Wnt1/C2mE transgenic mice model and reduce levels of CAD, DHODH, and PAICS in vivo. We demonstrate that DHAA exerts an anticancer effect on GC by targeting transcription factor FOXK2, reducing transcription of key genes for nucleotide metabolism and impairing nucleotide biosynthesis, thus DHAA is a promising candidate for GC therapy.

Enantioselective α-Boryl Carbene Transformations.

Carbenes, recognized as potent intermediates, enable unique chemical transformations, and organoborons are pivotal in diverse chemical applications. As a hybrid of carbene and the boryl group, α-boryl carbenes are promising intermediates for the construction of organoborons; unfortunately, such carbenes are hard to access and have low structural diversity with their asymmetric transformations largely uncharted. In this research, we utilized boryl cyclopropenes as precursors for the swift synthesis of α-boryl metal carbenes, a powerful category of intermediates for chiral organoboron synthesis. These α-boryl carbenes undergo a series of highly enantioselective transfer reactions, including B-H and Si-H insertion, cyclopropanation, and cyclopropanation/Cope rearrangement, catalyzed by a singular chiral copper complex. This approach opens paths to previously unattainable but easily transformable chiral organoborons, expanding both carbene and organoboron chemistry.

UHMK1 promotes gastric cancer progression through reprogramming nucleotide metabolism.

UHMK1 is a nuclear serine/threonine kinase recently implicated in carcinogenesis. However, the functions and action mechanisms of UHMK1 in the pathogenesis of human gastric cancer (GC) are unclear. Here, we observed that UHMK1 was markedly upregulated in GC. UHMK1 silencing strongly inhibited GC aggressiveness. Interestingly, UHMK1-induced GC progression was mediated primarily via enhancing de novo purine synthesis because inhibiting purine synthesis reversed the effects of UHMK1 overexpression. Mechanistically, UHMK1 activated ATF4, an important transcription factor in nucleotide synthesis, by phosphorylating NCOA3 at Ser (S) 1062 and Thr (T) 1067. This event significantly enhanced the binding of NCOA3 to ATF4 and the expression of purine metabolism-associated target genes. Conversely, deficient phosphorylation of NCOA3 at S1062/T1067 significantly abrogated the function of UHMK1 in GC development. Clinically, Helicobacter pylori and GC-associated UHMK1 mutation induced NCOA3-S1062/T1067 phosphorylation and enhanced the activity of ATF4 and UHMK1. Importantly, the level of UHMK1 was significantly correlated with the level of phospho-NCOA3 (S1062/T1067) in human GC specimens. Collectively, these results show that the UHMK1-activated de novo purine synthesis pathway significantly promotes GC development.

Staphylococcal enterotoxin B exposed to pregnant rats inhibits the hedgehog signaling pathway in thymic T lymphocytes of the offspring.

The Hedgehog (Hh) signaling pathway is involved in T cell differentiation and development and plays a major regulatory part in different stages of T cell development. A previous study by us suggested that prenatal exposure to staphylococcal enterotoxin B (SEB) changed the percentages of T cell subpopulation in the offspring thymus. However, it is unclear whether prenatal SEB exposure impacts the Hh signaling pathway in thymic T cells. In the present study, pregnant rats at gestational day 16 were intravenously injected once with 15 µg SEB, and the thymi of both neonatal and adult offspring rats were aseptically acquired to scrutinize the effects of SEB on the Hh signaling pathway. It firstly found that prenatal SEB exposure clearly caused the increased expression of Shh and Dhh ligands of the Hh signaling pathway in thymus tissue of both neonatal and adult offspring rats, but significantly decreased the expression levels of membrane receptors of Ptch1 and Smo, transcription factor Gli1, as well as target genes of CyclinD1, C-myc, and N-myc in Hh signaling pathway of thymic T cells. These data suggest that prenatal SEB exposure inhibits the Hh signaling pathway in thymic T lymphocytes of the neonatal offspring, and this effect can be maintained in adult offspring via the imprinting effect.

Relationship among subjective exercise experience, exercise behavior, and trait anxiety in adolescents.

OBJECTIVE: To investigate the influence of subjective exercise experience on adolescent trait anxiety and to reveal the mediating effect of exercise behavior. METHODS: Using the Subjective Exercise Experience Scale (SEES), Physical Exercise Rating Scale (PARS-3), and Trait Anxiety Inventory (T-AI), a questionnaire survey was conducted among 500 adolescents in Southwest China, and the SPSS21.0 and AMOS21.0 statistical analysis software was used to statistics and analysis on the questionnaires. RESULTS: 1) Among adolescents, the exercise behavior of boys was significantly higher than that of girls (p < 0.05), and the subjective exercise experience of students aged 9 to 12 was significantly higher than that of students aged 12 to 15 (p < 0.05). 2) The subjective exercise experience could directly and positively predict exercise behavior (ß = 0.45, p < 0.001) and negatively predict trait anxiety (ß = -0.26, p < 0.05), and exercise behavior could directly and negatively predict trait anxiety (ß = -0.32, p < 0.01). 3) The exercise behavior played a partial mediating effect between subjective exercise experience and trait anxiety (the mediation effect was -0.14). Among them, compared with low- and high-exercise amounts, the exercise behavior of moderate exercise amounts had the strongest mediating effect between subjective exercise experience and trait anxiety. CONCLUSION: The good subjective exercise experience not only has direct benefits for improving trait anxiety in adolescents but also helps to improve their exercise behavior, enrich daily physical exercise activities, and indirectly promote the reduction of trait anxiety.

Machine Learning in Unmanned Systems for Chemical Synthesis.

Chemical synthesis is state-of-the-art, and, therefore, it is generally based on chemical intuition or experience of researchers. The upgraded paradigm that incorporates automation technology and machine learning (ML) algorithms has recently been merged into almost every subdiscipline of chemical science, from material discovery to catalyst/reaction design to synthetic route planning, which often takes the form of unmanned systems. The ML algorithms and their application scenarios in unmanned systems for chemical synthesis were presented. The prospects for strengthening the connection between reaction pathway exploration and the existing automatic reaction platform and solutions for improving autonomation through information extraction, robots, computer vision, and intelligent scheduling were proposed.

Period 2 Suppresses the Malignant Cellular Behaviors of Colorectal Cancer Through the Epithelial-Mesenchymal Transformation Process.

INTRODUCTION: The PER2 (Period circadian regulator 2) gene is related to the circadian clock, and it has been deemed as a suppressor gene in osteosarcoma and lung carcinoma. However, the part of PER2 in CRC (colorectal cancer) needs to be further determined. METHODS: First, we collected clinical samples to detect PER2 expression in CRC. Then, we used cell transfection to knock down PER2 expression in CRC cell lines and performed a series of functional experiments to elucidate the effects of PER2 on CRC cells. We next verified whether PER2 affects the epithelial-mesenchymal transformation (EMT) process in CRC by conducting quantitative real-time PCR and western blotting. RESULTS: In the research, we revealed that the expression of PER2 decreased in CRC clinical samples. In addition, knocking down PER2 expression caused CRC cells to acquire malignant biological features. Finally, we found that PER2 knockdown may activate the Snail/Slug axis through inhibiting p53, therefore promote the activation of the EMT pathway. CONCLUSION: In conclusion, low PER2 expression reinforces migration and activates EMT in CRC, suggesting that PER2 is closely related to CRC development and could be used as a potential treatment site in the clinic.

Highly Regioselective Cobalt-Catalyzed Hydroboration of Internal Alkynes.

Herein, we report the development of new Co complexes that have cyclopropane-based diphosphine ligands and can catalyze highly chemo-, regio-, and stereoselective hydroboration reactions of unsymmetrical internal alkynes. These reactions exhibited unusual regioselectivity: specifically, reactions of aryl alkyl internal alkynes showed excellent cis-ß-addition selectivity, and reactions of dialkyl internal alkynes gave excellent cis-α-addition selectivity. Highly regioselective hydroboration of unsymmetrical dialkyl internal alkynes cannot be achieved by other known methods. The reactions described herein are highly synthetically useful, particularly for the stereoselective synthesis of trisubstituted alkenylborates and alkenes. Mechanistic studies indicate that a CoI -H species is a plausible active catalyst and the rigid structure of the cyclopropane skeleton of the ligands and the crowded reaction pocket were responsible for the unprecedented regioselectivity.

Identification of crucial genes of pyrimidine metabolism as biomarkers for gastric cancer prognosis.

BACKGROUND: Metabolic reprogramming has been reported in various kinds of cancers and is related to clinical prognosis, but the prognostic role of pyrimidine metabolism in gastric cancer (GC) remains unclear. METHODS: Here, we employed DEG analysis to detect the differentially expressed genes (DEGs) in pyrimidine metabolic signaling pathway and used univariate Cox analysis, Lasso-penalizes Cox regression analysis, Kaplan-Meier survival analysis, univariate and multivariate Cox regression analysis to explore their prognostic roles in GC. The DEGs were experimentally validated in GC cells and clinical samples by quantitative real-time PCR. RESULTS: Through DEG analysis, we found NT5E, DPYS and UPP1 these three genes are highly expressed in GC. This conclusion has also been verified in GC cells and clinical samples. A prognostic risk model was established according to these three DEGs by Univariate Cox analysis and Lasso-penalizes Cox regression analysis. Kaplan-Meier survival analysis suggested that patient cohorts with high risk score undertook a lower overall survival rate than those with low risk score. Stratified survival analysis, Univariate and multivariate Cox regression analysis of this model confirmed that it is a reliable and independent clinical factor. Therefore, we made nomograms to visually depict the survival rate of GC patients according to some important clinical factors including our risk model. CONCLUSION: In a word, our research found that pyrimidine metabolism is dysregulated in GC and established a prognostic model of GC based on genes differentially expressed in pyrimidine metabolism.

Dual-Specificity Tyrosine Phosphorylation-Regulated Kinase 3 Loss Activates Purine Metabolism and Promotes Hepatocellular Carcinoma Progression.

Cancer cells metabolize different energy sources to generate biomass rapidly. The purine biosynthetic pathway was recently identified as an important source of metabolic intermediates for these processes. However, very little was known about the regulatory mechanisms of purine metabolism in hepatocellular carcinoma (HCC). We explored the role of dual-specificity tyrosine (Y) phosphorylation-regulated kinase 3 (Dyrk3) in HCC metabolism. Dyrk3 was significantly down-regulated in HCC compared with normal controls. Its introduction in HCC cells markedly suppressed tumor growth and metastasis in xenograft tumor models. Mass spectrometric analysis of metabolites suggests that the effect of Dyrk3 on HCC occurred at least partially through down-regulating purine metabolism, as evidenced by the fact that inhibiting purine synthesis reverted the HCC progression mediated by the loss of Dyrk3. We further provide evidence that this action of Dyrk3 knockdown requires nuclear receptor coactivator 3 (NCOA3), which has been shown to be a coactivator of activating transcription factor 4 (ATF4) to target purine pathway genes for transcriptional activation. Mechanistically, Dyrk3 directly phosphorylated NCOA3 at Ser-1330, disrupting its binding to ATF4 and thereby causing the inhibition of ATF4 transcriptional activity. However, the phosphorylation-resistant NCOA3-S1330A mutant has the opposite effect. Interestingly, the promoter activity of Dyrk3 was negatively regulated by ATF4, indicating a double-negative feedback loop. Importantly, levels of Dyrk3 and phospho-NCOA3-S1330 inversely correlate with the expression of ATF4 in human HCC specimens. Conclusion: Our findings not only illustrate a function of Dyrk3 in reprograming HCC metabolism by negatively regulating NCOA3/ATF4 transcription factor complex but also identify NCOA3 as a phosphorylation substrate of Dyrk3, suggesting the Dyrk3/NCOA3/ATF4 axis as a potential candidate for HCC therapy.

Etoposide induced NMI promotes cell apoptosis by activating the ARF-p53 signaling pathway in lung carcinoma.

Lung carcinoma is one of the leading causes of cancer-related death. The N-Myc and STATs interactor (NMI) has been reported to take participate in lots of physiological processes, but the involvement and functional mechanisms of NMI in lung carcinoma are poorly understood. In this study, we found that etoposide induces proliferation suppression, cell apoptosis and increases caspase-3 activity in A549 cells. Furthermore, etoposide treatment up-regulates the expression of NMI and ARF, enhances the interaction of NMI and ARF and promotes the p53 transcriptional activities. By contrast, when silencing NMI, the proliferation suppression and cell apoptosis caused by etoposide were repressed and the p53 signaling pathway activation was also suppressed. These investigations demonstrated etoposide-induced NMI can suppress tumor proliferation and promote cell apoptosis by activating the ARF-p53 signaling pathway in lung carcinoma. Our results provide an alternative mechanism for etoposide in lung carcinoma and suggest NMI has a critical role in suppressing lung carcinoma progression.

Tannic acid inhibits NLRP3 inflammasome-mediated IL-1ß production via blocking NF-κB signaling in macrophages.

The NLRP3 inflammasome rapidly responds to many infections and stress signals and is involved in the pathogenesis of numerous inflammatory disease processes. Tannic acid plays a role in antioxidant, antifungal and antitumor activities. Here, we reported that tannic acid inhibited NLRP3 inflammasome activation by blocking NF-κB signaling to suppress IL-1ß secretion. We found that the BMDMs (bone marrow-derived macrophages cells) pre-treated with tannic acid blocked caspase-1 cleavage and inhibited IL-1ß secretion in a NLRP3-dependent manner, and suppressed NF-κB signaling activation by inhibiting NF-κB/P65 nuclear localization, suggesting that tannic acid inhibited NLRP3 inflammasome activation. These investigations revealed that tannic acid inhibited NLRP3 inflammasome activation via blocking NF-κB signaling in macrophages, providing us with evidence that tannic acid may be a potent inhibitor for NLRP3-driven diseases.

3D FRP Reinforcement Systems for Concrete Beams: Innovation towards High Performance Concrete Structures.

Despite the advantages of using lightweight and non-corrosive carbon fiber reinforced polymer (CFRP) reinforcements in concrete structures, their widespread adoption has been limited due to concerns regarding the brittle failure of CFRP rupture and its relatively softer load-deflection stiffness. This work offers logical solutions to these two crucial problems: using aggregate coating to strengthen the CFRP-concrete bond and ultimately the load-deflection stiffness, and using CFRP-concrete debonding propagation to create pseudo-ductile behavior. Subsequently, the concrete cracking behavior, the apparent CFRP modulus with aggregates, and the post-peak capacity and deflection of three-dimensional (3D) CFRP-reinforced concrete are all described by equations derived from experiments. These formulas will be helpful in the future design of non-prismatic concrete components for low-impact building projects. The potential of this innovative design scheme in terms of increased capacity and deflections with less concrete material is demonstrated through comparisons between non-prismatic CFRP-reinforced concrete and measured steel reinforced equivalency.

OGNNMDA: a computational model for microbe-drug association prediction based on ordered message-passing graph neural networks.

In recent years, many excellent computational models have emerged in microbe-drug association prediction, but their performance still has room for improvement. This paper proposed the OGNNMDA framework, which applied an ordered message-passing mechanism to distinguish the different neighbor information in each message propagation layer, and it achieved a better embedding ability through deeper network layers. Firstly, the method calculates four similarity matrices based on microbe functional similarity, drug chemical structure similarity, and their respective Gaussian interaction profile kernel similarity. After integrating these similarity matrices, it concatenates the integrated similarity matrix with the known association matrix to obtain the microbe-drug heterogeneous matrix. Secondly, it uses a multi-layer ordered message-passing graph neural network encoder to encode the heterogeneous network and the known association information adjacency matrix, thereby obtaining the final embedding features of the microbe-drugs. Finally, it inputs the embedding features into the bilinear decoder to get the final prediction results. The OGNNMDA method performed comparative experiments, ablation experiments, and case studies on the aBiofilm, MDAD and DrugVirus datasets using 5-fold cross-validation. The experimental results showed that OGNNMDA showed the strongest prediction performance on aBiofilm and MDAD and obtained sub-optimal results on DrugVirus. In addition, the case studies on well-known drugs and microbes also support the effectiveness of the OGNNMDA method. Source codes and data are available at: https://github.com/yyzg/OGNNMDA.

Genomic Characteristics of Okamejei kenojei and the Implications to Its Evolutionary Biology Study.

Okamejei kenojei is an important economic species widely distributed in shallow coastal waters of the western North Pacific. In this study, the whole-genome survey analysis of O. kenojei was conducted to reveal its genomic characteristics. The genome size was estimated to be 2027.44 Mb, the repeat sequence content was 44.90%, and the heterozygous ratio was 1.04%. The mitochondrial genome excavated from the sequencing data was 16,974 bp, and it can form the closed circular molecule. The phylogenetic tree based on 13 protein-coding gene sequences supported the validity of Okamejei and assisted the conclusion that Raja porosa was the junior synonym of O. kenojei. Plenty of potential microsatellite loci were identified, and the distribution frequency was estimated to be approximately 236.3 SSRs per Mb. Among all motif types of microsatellites, the dinucleotide repeats were dominant (82.59%), followed by the trinucleotide repeats (8.05%), tetranucleotide repeats (5.80%), pentanucleotide repeats (2.83%), and hexanucleotide repeats (0.72%). The results of the present study could not only provide useful information for understanding the genome structure and functional characteristics of O. kenojei, but also lay the foundation for the subsequent mapping of the whole genome.

Theoretical Study for Adsorption-Diffusion on H-MOR and Pyridine Pre-adsorbed H-MOR of Dimethyl Ether Carbonylation.

For dimethyl ether (DME) carbonylation, pyridine pre-adsorbed hydrogen mordenite (H-MOR) is beneficial to prolonging the catalyst life. The adsorption and diffusion behaviors on periodic models H-AlMOR and H-AlMOR-Py were simulated. The simulation was based on Monte Carlo and molecular dynamics. The following conclusions were drawn from the simulation results. The adsorption stability of CO in 8-MR is increased, and the adsorption density of CO in 8-MR is more concentrated on H-AlMOR-Py. 8-MR is the main active site for DME carbonylation, so the introduction of pyridine would be beneficial for the main reaction. The adsorption distributions of methyl acetate (MA) (in 12-MR) and H2O on H-AlMOR-Py are significantly decreased. It means the product MA and the byproduct H2O are more easily desorbed on H-AlMOR-Py. For the mixed feed of DME carbonylation, the feed ratio (PCO/PDME) must reach 50:1 on H-AlMOR so that the reaction molar ratio can reach the theoretical value (NCO/NDME ≈ 1:1), while the feed ratio on H-AlMOR-Py is only up to 10:1. Thus, the feed ratio can be adjusted, and raw materials can reduce consumption. In conclusion, H-AlMOR-Py can improve the adsorption equilibrium of reactants CO and DME and increase the concentration of CO in 8-MR.

Prenatal Exposure of Rats to Staphylococcal Enterotoxin B Alters the Expression of Th1 and Th2 Cytokines via Decreased Methylation in the Spleen of Adult but not Neonatal Offspring.

BACKGROUND: The methylation of IFN-γ and IL-4 genes is regarded as an epigenetic regulation that maintains the Th1 or Th2 phenotype. OBJECTIVE: To explore the influence of prenatal administration of the staphylococcal enterotoxin B (SEB) in pregnant rats, on the IFN-γ or IL-4 expression in the offspring spleen. METHODS: The SEB or PBS was administered intravenously to pregnant rats on the embryo-day 16. After normal delivery, the spleens from the fifth-day neonates and adult offspring were isolated under anesthesia. Quantitative PCR, western blot, ELISA and MeDIP-qPCR were applied to determine the levels of the splenic IFN-γ or IL-4 mRNAs, their protein levels, and methylation status, respectively. RESULTS: Prenatal administration of the SEB in pregnant rats decreased the levels of the splenic IFN-γ and IL-4 proteins in neonates, but increased their mRNA levels. However, prenatal administration of the SEB significantly augmented both mRNA and protein levels of the IFN-γ and IL-4 in the adult spleen. In addition, the prenatal SEB administration decreased the methylation of the splenic IFN-γ and IL-4 in adult but not neonatal offspring. CONCLUSION: The prenatal administration of SEB in pregnant rats can cause a mixed Th1 and Th2 cytokines response in the offspring spleen, and alter the cytokine expression of the Th1 and Th2 via decreasing the methylation in adult but, not neonatal offspring spleen.

Online and Unsupervised Anomaly Detection for Streaming Data Using an Array of Sliding Windows and PDDs.

In this article, we propose an online and unsupervised anomaly detection algorithm for streaming data using an array of sliding windows and the probability density-based descriptors (PDDs) (based on these windows). This algorithm mainly consists of three steps: 1) we use a main sliding window over streaming data and segment this window into an array of nonoverlapping subwindows; 2) we propose the PDDs with dimension reduction, based on the kernel density estimation, to estimate the probability density of data in each subwindow; and 3) we design the distance-based anomaly detection rule to determine whether the current observation is anomalous. The experimental results and performances are presented based on the Numenta anomaly benchmark. Compared with the anomaly detection algorithm using the hierarchical temporal memory proposed by Numenta (which outperforms a wide range of other anomaly detection algorithms), our algorithm can perform better in many cases, that is, with higher detection rates and earlier detection for contextual anomalies and concept drifts.

Candida albicans disorder is associated with gastric carcinogenesis.

Background: Bacterial infection is associated with gastric carcinogenesis. However, the relationship between nonbacterial components and gastric cancer (GC) has not been fully explored. We aimed to characterize the fungal microbiome in GC. Methods: We performed ITS rDNA gene analysis in cancer lesions and adjacent noncancerous tissues of 45 GC cases from Shenyang, China. Obtaining the OTUs and combining effective grouping, we carried out species identifications, alpha and beta diversity analyses, and FUNGuild functional annotation. Moreover, differences were compared and tested between groups to better investigate the composition and ecology of fungi associated with GC and find fungal indicators. Results: We observed significant gastric fungal imbalance in GC. Principal component analysis revealed separate clusters for the GC and control groups, and Venn diagram analysis indicated that the GC group showed a lower OTU abundance than the control. At the genus level, the abundances of 15 fungal biomarkers distinguished the GC group from the control, of which Candida (p = 0.000246) and Alternaria (p = 0.00341) were enriched in GC, while Saitozyma (p = 0.002324) and Thermomyces (p = 0.009158) were decreased. Combining the results of Welch's t test and Wilcoxon rank sum test, Candida albicans (C. albicans) was significantly elevated in GC. The species richness Krona pie chart further revealed that C. albicans occupied 22% and classified GC from the control with an area under the receiver operating curve (AUC) of 0.743. Random forest analysis also confirmed that C. albicans could serve as a biomarker with a certain degree of accuracy. Moreover, compared with that of the control, the alpha diversity index was significantly reduced in the GC group. The Jaccard distance index and the Bray abundance index of the PCoA clarified separate clusters between the GC and control groups at the species level (p = 0.00051). Adonis (PERMANOVA) analysis and ANOVA showed that there were significant differences in fungal structure among groups (p = 0.001). Finally, FUNGuild functional classification predicted that saprotrophs were the most abundant taxa in the GC group. Conclusions: This study revealed GC-associated mycobiome imbalance characterized by an altered fungal composition and ecology and demonstrated that C. albicans can be a fungal biomarker for GC. With the significant increase of C. albicans in GC, the abundance of Fusicolla acetilerea, Arcopilus aureus, Fusicolla aquaeductuum were increased, while Candida glabrata, Aspergillus montevidensis, Saitozyma podzolica and Penicillium arenicola were obviously decreased. In addition, C. albicans may mediate GC by reducing the diversity and richness of fungi in the stomach, contributing to the pathogenesis of GC.

Inhibition of protein PMP22 enhances etoposide-induced cell apoptosis by p53 signaling pathway in Gastric Cancer.

Gastric Cancer (GC) is one of the main causes leading to death. PMP22, as a member of the GAS3 family of tetraspan proteins, it is associated with a variety of neurological diseases. Recently, more and more studies have shown that PMP22 play a great role in the physiological processes such as cells adhesion, migration, proliferation and tumorigenesis, but the involvement and functional mechanisms of PMP22 in Gastric carcinoma are not investigated clearly. In this study, we found that the PMP22 was overexpressed in the GC cells and tissue. Knockdown of PMP22 inhibits cell growth. Over-expressed PMP22 inhibits the etoposide-induced apoptosis, meanwhile knockdown of PMP22 promotes the etoposide-induced proliferation suppression, and increases cell apoptosis in GC cells. Furthermore, PMP22 enhanced the inhibition of the p53 transcriptional activities and down-regulated the p53 targeting genes, including p21, BAX and PUMA with or without treatment of etoposide. Finally, our results showed that PMP22 reduced the etoposide-induced tumor growth suppression in nude mice. Taken together, our research provided an anti-apoptotic properties alternative mechanism for PMP22 in gastric carcinoma and suggested PMP22 can be a potential target for the treatment of gastric cancer.