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Polyethylene (PE) pipes are widely used in urban gas transportation due to their good toughness and corrosion resistance. Currently, the designed service life of a PE pipeline is 50 years, and some urban gas PE pipelines are approaching their service life. However, research on the aging assessment of PE pipelines is not complete, and it is impossible to effectively predict their aging status in service. Once urban gas PE pipelines are damaged, serious accidents may be caused. PE80 and PE100 pipelines are commonly used for urban gas, and improved accelerated aging tests were conducted considering different conditions of pressure, pipe diameter, and temperature. According to the experimental results, an aging life prediction method for PE pipes was constructed based on the Arrhenius formula considering multiple effect factors.

Abstract To improve the blockchain consensus algorithm practical Byzantine fault tolerance (PBFT) with random master node selection, which has high communication overhead and a small supported network size, this paper proposes a Byzantine fault tolerant consensus algorithm based on credit (CBFT) enhanced with a grouping and credit model. The CBFT algorithm divides the network nodes according to the speed of their response to the management nodes, resulting in different consensus sets, and achieves consensus within and outside the group separately to reduce communication overhead and increase system security. Second, the nodes are divided into different types according to the credit model, each with different responsibilities to reduce the probability that the master node is a malicious node. Experimental results show that the throughput of the CBFT algorithm is 3.1 times that of PBFT and 1.5 times that of GPBFT when the number of nodes is 52. Our scheme has latency that is 7.4% that of PBFT and 38.8% that of GPBFT; CBFT has communication overhead that is 6.4% that of PBFT and 87.3% that of GPBFT. The number of nodes is 300, and the Byzantine fault tolerance is improved by 59.3%. These improvements are clearer with the increase in the number of nodes.

Abstract Prolonged activation of nuclear factor (NF)-кB signaling significantly contributes to the development of colorectal cancer (CRC). New therapeutic opportunities are emerging from targeting this distorted cell signaling transduction. Here, we discovered the critical role of RING finger 138 (RNF138) in CRC tumorigenesis through regulating the NF-кB signaling, which is independent of its Ubiquitin-E3 ligase activity involved in DNA damage response. RNF138−/− mice were hyper-susceptible to the switch from colitis to aggressive malignancy, which coincided with sustained aberrant NF-кB signaling in the colonic cells. Furthermore, RNF138 suppresses the activation of NF-кB signaling pathway through preventing the translocation of NIK and IKK-Beta Binding Protein (NIBP) to the cytoplasm, which requires the ubiquitin interaction motif (UIM) domain. More importantly, we uncovered a significant correlation between poor prognosis and the downregulation of RNF138 associated with reinforced NF-кB signaling in clinical settings, raising the possibility of RNF138 dysregulation as an indicator for the therapeutic intervention targeting NF-кB signaling. Using the xenograft models built upon either RNF138-dificient CRC cells or the cells derived from the RNF138-dysregulated CRC patients, we demonstrated that the inhibition of NF-кB signaling effectively hampered tumor growth. Overall, our work defined the pathogenic role of aberrant NF-кB signaling due to RNF138 downregulation in the cascade events from the colitis switch to colonic neoplastic transformation and progression, and also highlights the possibility of targeting the NF-кB signaling in treating specific subtypes of CRC indicated by RNF138-ablation.

Shikonin derivatives are natural naphthoquinone compounds and the main bioactive components produced by several boraginaceous plants, such as Lithospermum erythrorhizon and Arnebia euchroma. Phytochemical studies utilizing both L. erythrorhizon and A. euchroma cultured cells indicate the existence of a competing route branching out from the shikonin biosynthetic pathway to shikonofuran. A previous study has shown that the branch point is the transformation from (Z)-3’’-hydroxy-geranylhydroquinone to an aldehyde intermediate (E)-3’’-oxo-geranylhydroquinone. However, the gene encoding the oxidoreductase that catalyzes the branch reaction remains unidentified. In this study, we discovered a candidate gene belonging to the cinnamyl alcohol dehydrogenase family, AeHGO, through coexpression analysis of transcriptome data sets of shikonin-proficient and shikonin-deficient cell lines of A. euchroma. In biochemical assays, purified AeHGO protein reversibly oxidized (Z)-3’’-hydroxy-geranylhydroquinone to produce (E)-3’’-oxo-geranylhydroquinone followed by reversibly reducing (E)-3’’-oxo-geranylhydroquinone to (E)-3’’-hydroxy-geranylhydroquinone, resulting in an equilibrium mixture of the three compounds. Time course analysis and kinetic parameters showed that the reduction of (E)-3’’-oxo-geranylhydroquinone was stereoselective and efficient in presence of NADPH, which determined that the overall reaction proceeded from (Z)-3’’-hydroxy-geranylhydroquinone to (E)-3’’-hydroxy-geranylhydroquinone. Considering that there is a competition between the accumulation of shikonin and shikonofuran derivatives in cultured plant cells, AeHGO is supposed to play an important role in the metabolic regulation of the shikonin biosynthetic pathway. Characterization of AeHGO should help expedite the development of metabolic engineering and synthetic biology toward production of shikonin derivatives.

According to the geographical boundaries, we divided the Yangtze river basin into nine sub-basins, and calculated areal rainfall in each sub-basin based on monthly precipitation data at 700 meteorological stations in the basin from 1961 to 2017. We find threshold values of extreme precipitation climate events in each sub-basin by percentile method after applying Box-Cox transformation. The results show that compared with year number ranking method, the threshold value of extreme precipitation climate events in the Yangtze sub-basins defined by these normalized areal rainfall series have obvious advantage. It presents a more stable characteristic when the length of the areal rainfall series changes. The threshold value changes are reduced, and the threshold changes for vast majority of the sub-basins are within 10 mm. Thus the extreme years are stable. Using the threshold values by this method, we examined whether extreme precipitation climate events have occurred during flood season in 2018. As a result, extreme rainy climate event happens in the Mintuo river basin and extreme less rain climate events happen both in the stem stream from Chongqing to Yichang and in the basin that from Hanjiang river to the middle reaches of the Yangtze river.

The traditional Chinese medicine plant Fallopia multiflora (Thunb.) Harald. contains various pharmacodynamically active glycosides, such as stilbene glycosides, anthraquinone (AQ) glycosides, and flavonoid glycosides. Glycosylation is an important reaction in plant metabolism that is generally completed by glycosyltransferase in the last step of the secondary metabolite biosynthesis pathway, and it can improve the beneficial properties of many natural products. In this study, based on the transcriptome data of F. multiflora, we cloned two Uridine-diphosphate-dependent glycosyltransferases (UGTs) from the cDNA of F. multiflora (FmUGT1 and FmUGT2). Their full-length sequences were 1602 and 1449 bp, encoding 533 and 482 amino acids, respectively. In vitro enzymatic reaction results showed that FmUGT1 and FmUGT2 were promiscuous and could catalyze the glycosylation of 12 compounds, including stilbenes, anthraquinones, flavonoids, phloretin, and curcumin, and we also obtained and structurally identified 13 glycosylated products from both of them. Further experiments on the in vivo function of FmUGT1 and FmUGT2 showed that 2, 3, 5, 4’- tetrahydroxy stilbene-2-O-β-d-glucoside (THSG) content in hairy roots was elevated significantly when FmUGT1 and FmUGT2 were overexpressed and decreased accordingly in the RNA interference (RNAi) groups. These results indicate that FmUGT1 and FmUGT2 were able to glycosylate a total of 12 structurally diverse types of acceptors and to generate O-glycosides. In addition, FmUGT1 and FmUGT2 efficiently catalyzed the biosynthesis of THSG, and promoted the production of AQs in transgenic hairy roots.

ObjectivesAbdominal aortic aneurysm (AAA) is a cardiovascular disease with high mortality and pathogenesis closely related to various cell death types, e.g., autophagy, apoptosis and pyroptosis. However, the association between AAA and ferroptosis is unknown.MethodsGSE57691 and GSE98278 dataset were obtained from the Gene Expression Omnibus database, and a ferroptosis-related gene (FRG) set was downloaded from the FerrDb database. These data were normalized, and ferroptosis-related differentially expressed genes (FDEGs, AAA vs. normal samples) were identified using the limma package in R. FRGs expression was analyzed by Gene Set Expression Analysis (GSEA), and FDEGs were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes (KEGG) pathway enrichment analyses using the clusterProfiler package in R and ClueGO in Cytoscape. Protein–protein interaction networks were assembled using Cytoscape, and crucial FDEGs were identified using CytoHubba. Critical FDEG transcription factors (TFs) were predicted with iRegulon. FDEGs were verified in GSE98278 set, and key FDEGs in AAA (compared with normal samples) and ruptured AAA (RAAA; compared with AAA samples) were identified. Ferroptosis-related immune cell infiltration and correlations with key genes were analyzed by CIBERSORT. Key FEDGs were reverified in Ang II-induced AAA models of ApoE–/– and CD57B/6J mice by immunofluorescence assay.ResultsIn AAA and normal samples, 40 FDEGs were identified, and the expression of suppressive FRGs was significantly downregulated with GSEA. For FDEGs, the GO terms were response to oxidative stress and cellular response to external stimulus, and the KEGG pathways were the TNF and NOD-like receptor signaling pathways. IL6, ALB, CAV1, PTGS2, NOX4, PRDX6, GPX4, HSPA5, HSPB1, and NCF2 were the most enriched genes in the crucial gene cluster. CEBPG, NFAT5, SOX10, GTF2IRD1, STAT1, and RELA were potential TFs affecting these crucial genes. Ferroptosis-related immune cells involved in AAA formation were CD8+ T, naive CD4+ T, and regulatory T cells (Tregs); M0 and M2 macrophages; and eosinophils. Tregs were also involved in RAAA. GPX4, SLC2A1, and PEBP1 expression was downregulated in both the RAAA and AAA samples. GPX4 and PEBP1 were more important in AAA because they influenced ferroptosis-related immune cell infiltration, and SLC2A1 was more important in RAAA.ConclusionsThis is the first study to show that ferroptosis is crucial to AAA/RAAA formation. The TNF and NOD-like signaling pathways and ferroptosis-related immune cell infiltration play key roles in AAA/RAAA. GPX4 is a key ferroptosis-related gene in AAA. Ferroptosis and related genes might be promising targets in the treatment of AAA/RAAA.

Nitrogen (N) strongly affects plant growth and metabolism. Although ammonium toxicity has been reported, the effects of nitrogen on shikonin biosynthesis remain obscure. In this study, we tested four different concentrations of NH4+ on Arnebia euchroma hairy roots (AEHR) to clarify the influence of NH4+ on the growth of AEHR and on shikonin accumulation in them and the possible mechanisms. The results showed that compared with the 0% NH4+ treatment (only nitrate as a nitrogen source), the 10% NH4+ treatment increased the fresh weight and the dry weight of AEHR and promoted the synthesis of shikonins. In contrast, the 20% NH4+ treatment started to show inhibition effects on the growth of and shikonin accumulation in AEHR, and the 30% NH4+ treatment exhibited the strongest inhibition effects. With an increased percentage of NH4+, the AEHR became shorter and thicker, with more branches. To further elucidate the mechanisms, we analyzed the time course of nitrogen assimilation, the gene expression level of key enzymes involved in shikonin biosynthesis pathway, and the content of various endogenous hormones in the presence of toxic NH4+ concentrations. The results indicated that auxin and cytokinin might regulate the growth and architecture of AEHR under NH4+ toxicity and revealed that the jasmonate level was reduced along with the inhibition of shikonin biosynthesis. This first comprehensive investigation of the effects of the ammonium/nitrate ratio on shikonin biosynthesis not only provides valuable data for optimizing the in vitro culture of A. euchroma and its shikonin production, but also suggests potential fertilizing strategies for its cultivation.

Abstract Background Systemic sclerosis (SSc) is an acquired autoimmune disorder characterized by excessive accumulation of collagen and progressive tissue fibrosis. Although interstitial lung disease (ILD) complicates the majority of SSc patients and is the leading cause of death, its pathogenesis remains largely unclear. In the current study, we aimed to evaluate the role of microRNAs in SSc-ILD. Methods miRNA expression patterns were assessed by miRNA array and real-time PCR from serum and PBMCs of SSc-ILD patients and healthy controls. Bleomycin-induced SSc-ILD mouse model was used to verify the miRNA expression in the lung tissue. The function of miRNAs in pulmonary fibroblasts was assessed using miRNA inhibitors, and mimics. Results miR-320a was significantly downregulated in both SSc-ILD patients and mouse models. The inhibition or overexpression of miR-320a in human pulmonary fibroblasts significantly affected the protein expression of type I collagen. Luciferase reporter assay, RT-PCR, and western blot analysis identified TGFBR2 and IGF1R as direct targets of miR-320a. Upon TGF-β stimulation, the expression of miR-320a and collagen genes were significantly upregulated. Conclusion miR-320a, together with its target genes, TGFBR2 and IGF1R, constituted a complex regulatory network, and played an important role in the fibrotic process of SSc-ILD. Investigation of more detailed mechanisms of miR-320a-mediated regulation of collagen expression may provide new therapeutic strategies for SSc-ILD.

Abstract To improve the seasonal prediction of monthly precipitation in summer over Northeast China (NEC), a hybrid prediction scheme is developed to combine the advantages of statistical method with dynamical prediction information from 4 coupled general climate models (CGCMs). As the operational prediction of summer climate is performed in March or earlier, the information of CGCMs employed in this study is from the hindcast/prediction in February for June and July, and March for August. Predictors comprise observations of the preceding winter sea surface temperature and simultaneous information derived from the CGCMs. Stability and multicollinearity are fully considered in predictor selection to avoid over‐fitting. For a single model, the monthly precipitation reconstructed from the predicted time series and the observed spatial load of the leading Empirical Orthogonal Function (EOF) modes with accumulative explained covariance more than 85%. For the multi‐model ensemble (MME), the predictions with the lowest correlation coefficient were removed until the performance of the MME was optimal for the cross‐validation period. This new ensemble method shows some advantages compared to a traditional MME method. The leave‐one‐out cross‐validation for 1982–2010 and the independent validation for 2011–2016 both indicate an improvement of the new hybrid scheme in seasonal predictions of summer monthly precipitation over NEC. The observed and predicted monthly precipitation are significantly correlated with coefficients of 0.71, 0.49, and 0.73, and their hit rates are 77%, 66%, and 77% for June, July, and August precipitation, respectively for the MME over the period 1982–2016.

BackgroundStriking similarities have been found between coronavirus disease 2019 (COVID-19) and anti-melanoma differentiation-associated gene 5 (MDA5) antibody (Ab)-related dermatomyositis, implying a shared autoinflammatory aberrance. Herein, we aim to investigate whether the anti-MDA5 Ab is present in COVID-19 and correlates with the severity and adverse outcome of COVID-19 patients.Methods and FindingsWe retrospectively recruited 274 adult inpatients with COVID-19 in this study, including 48, 164, and 62 cases of deaths, severe, and non-severe patients respectively. The anti-MDA5 Ab was determined by ELISA and verified by Western Blotting, which indicated that the positive rate of anti-MDA5 Ab in COVID-19 patients was 48.2% (132/274). The clinical and laboratory features, as well as outcomes between patients with positive and negative anti-MDA5 Ab were compared and we found that the anti-MDA5 Ab positive patients tended to represent severe disease (88.6% vs 66.9%, P

The Yunnan province of China is a typical humid region but with several severe region-wide droughts. Drought indices are generally used to identify and characterize drought events, and then play a key role in drought prediction. Therefore, a novel prediction model was proposed to predict a comprehensive drought indicator (meteorological composite index, MCI) in Yunnan province. This model combined the recurrent neural networks (RNN) based on a gated recurrent neural unit (GRU) and convolutional neural networks (CNN) with optimization using the modified particle swarm optimization (PSO) algorithm. In this model, pre-processed predictor data were input into the GRU module to extract the time features of the sequences. Furthermore, the feature matrices were input into the CNN module to extract the deep local features and the inter-relationship of the predictors. The model was trained and used to predict the monthly MCI drought index of the representative five stations of Yunnan province from 1960 to 2020. The combined model was evaluated by comparison with traditional machine learning models such as the least absolute shrinkage and selection operator (LASSO) and random forest (RF), and the traditional GRU model. The results show significantly improved skills in root mean square error, mean absolute error and Nash–Sutcliffe efficiency coefficient. This novel method was valuable for the monthly drought prediction in Yunnan province and related climate-risk management.

The 5p and 3p arms of microRNA (miRNA) are typically generated from the same precursor, and one arm influences protein output, while the other has a short half‐life. However, a few miR‐5p/3p pairs have been reported to co‐exist in cancer cells. Here, we performed a genome‐wide analysis of miRNA expression in gastric cancer (GC) cells to systematically investigate the co‐expression profile of miR‐5p/3p in gastric tumorigenesis. We discovered that only 41 miR‐5p/3p pairs out of 1749 analyzed miRNA were co‐expressed. Specifically, abnormal expression of miR‐369‐5p and miR‐369‐3p was correlated with GC progression. Importantly, both in vitro and in vivo assays revealed that miR‐369‐5p and miR‐369‐3p exhibited tumor‐suppressive roles by regulating jun proto‐oncogene and v‐akt murine thymoma viral oncogene homolog 1 function in GC cells, respectively. Moreover, we observed that miR‐369 was inactivated in GC tissues due to DNA methylation. We also showed that inhibition of miR‐369‐5p/3p attenuated the effect of azacitidine (AZA) treatment on suppressing cell growth and invasion. These results suggest that the therapeutic efficacy of AZA in GC is at least partly attributable to miR‐369 activation. Overall, our findings provide convincing evidence that both the 5p and 3p arms of miRNA co‐expressed in GC and DNA methylation‐induced miR‐369 signaling contribute to GC progression.

Fagopyrum dibotrys, being native to southwest China, is widely distributed in Yunnan, Guizhou Provinces and Chongqing City. However, the quality of medicinal materials growing in different origins varies greatly, and cannot meet the market demand for high-quality F. dibotrys. In this study, 648 metabolites were identified, and phenolic compounds of F. dibotrys from different origins were clearly separated by principal component analysis (PCA). Our results suggested that the medicinal differences of F. dibotrys from different origins can be elucidated via the variations in the abundance of the phenolic and flavonoid compounds. We found that the epicatechin, total flavonoids and total tannin content in Yunnan Qujing (YQ) and Yunnan Kunming (YK) were higher than those in Chongqing Shizhu (CS), Chongqing Fuling (CF) and Guizhou Bijie (GB), suggesting that Yunnan Province can be considered as one of the areas that produce high-quality medicinal materials. Additionally, 1,6-di-O-galloyl-β-D-glucose, 2,3-di-O-galloyl-D-glucose and gallic acid could be used as ideal marker compounds for the quality control of F. dibotrys from different origins caused by metabolites, and the F. dibotrys planted in Yunnan Province is well worth exploiting.

Gemcitabine serves as a first‐line chemotherapy agent for advanced pancreatic cancer (PC). However, the molecular basis by which gemcitabine exerts its effects is not well‐established, and the targeted genetic pathways remain unclear. Pvt1 oncogene (non‐protein coding) (PVT1) has been reported to be an oncogenic long non‐coding RNA in tumorigenesis. In the present study, we show that the expression of PVT1 is correlated with gemcitabine efficacy in PC therapy. Inhibition of PVT1 led to decreased cell growth in PC cells treated with gemcitabine. We also demonstrate that gemcitabine treatment decreases PVT1 levels and increases its encoded miRNAs, such as the miR‐1207 pair (miR‐1207‐5p/3p). Overexpression of the miR‐1207 pair enhanced the chemosensitivity of cells to gemcitabine, whereas silencing of miR‐1207‐5p/3p to prevent its induction by gemcitabine treatment led to increased cell growth. Mechanistic studies revealed that miR‐1207‐5p and miR‐1207‐3p target the SRC proto‐oncogene (non‐receptor tyrosine kinase) and ras homolog family member A in PC cells, respectively. In particular, we observed that gemcitabine induced Drosha ribonuclease III (Drosha) and DGCR8 microprocessor complex subunit (DGCR8) upregulation and then triggered PVT1 processing. Suppression of Drosha and DGCR8 contributed to a dampened efficacy of gemcitabine, indicating that gemcitabine decreased PVT1 expression by promoting its processing into miRNAs, which in turn resulted in blunted oncogenic signaling in PC cells. Moreover, we demonstrate that gemcitabine chemoresistance was a result of decreased expression of Drosha and DGCR8 in AsPC‐1 cells and tumor cell‐engrafted models. Overall, our findings define a novel mechanism for understanding the efficacy of gemcitabine chemotherapy in PC.

DDB1 and CUL4 associated factor 13 (DCAF13) is a protein coding gene located on chromosome 8q22.3, which is a hotspot amplified in various cancers. DCAF13 has been reported to be frequently amplified in breast cancer patients. However, the genetic alteration and potential role of DCAF13 in other cancers, including hepatocellular carcinoma, have not been investigated yet. In this study, we found that DCAF13 was amplified in 14.7% of the cases and its expression was upregulated (p < 0.001) in hepatocellular carcinoma samples in The Cancer Genome Atlas dataset. Increased expression of DCAF13 was also noticed in 40 paired hepatocellular carcinoma and adjacent non-tumor tissues both at messenger RNA and protein levels (p = 0.0002 and 0.0016, respectively). A positive relationship was observed between augmented DCAF13 levels and poorer tumor grade (p = 0.005), and we also found that hepatocellular carcinoma patients with increased DCAF13 expression in their tumors had significantly poorer survival compared with those with decreased DCAF13 expression (median survival time: 45.73 and 70.53 months, respectively). Multivariate Cox regression analysis showed that DCAF13 was an independent prognostic predictor of survival in hepatocellular carcinoma patients. Gene ontology and Kyoto Encyclopedia of Genes and genomes analysis indicated the potential role of DCAF13 as a crucial cell cycle regulator. Collectively, our findings revealed that the overexpression of DCAF13 in hepatocellular carcinoma was significantly associated with poor survival and may participate in the regulation of cell cycle progression.

BACKGROUND: MicroRNAs act as posttranscriptional regulators of gene expression in many biological processes. Their deregulations occur commonly in gastric cancer (GC). Although DNA methylation constitutes an important mechanism for microRNA deregulation in cancer, this field largely remains unexplored. METHODOLOGY/PRINCIPAL FINDINGS: Total RNA was extracted from the tissues of 100 patients with GC and four gastric cancer cell lines. The expression levels of miR-10a were determined by real-time PCR with specific TaqMan probes. Moreover, a functional analysis of miR-10a in regulating cell proliferation, migration and invasion was performed. Subsequently, quantitative methylation-specific PCR (qMSP) was used to detect the DNA methylation status in the CpG islands upstream of miR-10a. In this study, we found that the expression of miR-10a in GC cells was lower than that in normal cells, which was due to the hypermethylation of the CpG islands upstream of miR-10a. We also validated the slightly lower expression of miR-10a in GC tissues than their adjacent non-neoplastic tissues in 100 GC patients and confirmed the hypermethylation of CpG islands upstream of miR-10a in some patients. Furthermore, re-introduction of miR-10a into GC cells was able to inhibit cell proliferation, migration and invasion. Bioinformatic and immunoblot analysis indicated that the tumor suppressor roles of miR-10a in GC cells were possibly through targeting HOXA1. CONCLUSIONS/SIGNIFICANCE: Our data indicate that miR-10a acts as a tumor suppressor in GC cells and is partially silenced by DNA hypermethylation in GC, suggesting that miR-10a may serve as a potential diagnostic or therapeutic target of GC.

BACKGROUND AIMS: Gastric cancer is the most frequent gastrointestinal tumor in adults and is the most lethal form of human cancer. Despite of the improvements in treatments, the underlying mechanism of gastric carcinogenesis is not well known. To define novel modulators that regulate susceptibility to tumorgenesis, we focused on miR-219-2-3p. METHODS: Quantitative RT-PCR was employed to investigate the level of miR-219-2-3p in gastric cancer (GC) tissues (n = 113) and their matched adjacent normal tissues (n = 113). In vitro cell proliferation, apoptosis assays, cell migration, and invasion assays were performed to elucidate biological effects of miR-219-2-3p. Since silencing of miRNA by promoter CpG island methylation may be an important mechanism in tumorgenesis, GC cells were treated with 5-aza-2'-deoxycytidine and trichostatin A, and expression changes of miR-219-2-3p were subsequently examined by quantitative RT-PCR. Finally, the methylation status of CpG island upstream of miR-219-2-3p was analyzed by methylation-specific PCR in GC tissues (n = 22). RESULTS: miR-219-2-3p was down-regulated in GC and cell lines. In addition, the experiments documented the lower expression of miR-219-2-3p in GC specimens with higher grade and later stage tumors. Meanwhile, miR-219-2-3p exerted antiproliferative, proapoptotic, and antimetastatic roles and reduced levels of p-ERK1/2 in GC cells. Furthermore, 5-aza-2'-deoxycytidine and trichostatin A increased the expression (~2 fold) of miR-219-2-3p in GC cells. By methylation-specific PCR, DNA methylation in the upstream region of miR-219-2-3p was detected in both adjacent normal tissues and cancer tissues. As expected, the methylation level was considerably higher in the miR-219-2-3p down-regulated group than up-regulated group. CONCLUSIONS: miR-219-2-3p is potentially involved in gastric cancer progression and metastasis by regulating ERK1/2-related signal pathways, which may provide a novel therapeutic strategy for treatment of gastric cancer. Methylation mechanism may be involved in modulating the expression level of miR-219-2-3p in gastric cancer.