CPSF3 regulates alternative polyadenylation of CNIH2 to promote esophageal squamous cell carcinoma progression.

Alternative polyadenylation (APA), an important post-transcriptional regulatory mechanism, is aberrantly activated in cancer，but how APA functions in tumorigenesis remains elusive. We analyzed APA events in RNA-seq data in TCGA and reported 3'UTR alterations associated with esophageal squamous cell carcinoma (ESCC) patient prognosis and gene expression changes involving loss of tumor-suppressive miRNA binding sites. Moreover, we investigated the expression and function of cleavage and polyadenylation specific factor 3 (CPSF3), a key APA regulator in ESCC. By immunohistochemistry and qRT-PCR, we found that CPSF3 was highly expressed in ESCC tissues and associated with poor patient prognosis. Overexpression of CPSF3 enhanced, while knockdown of CPSF3 inhibited ESCC cell proliferation and migration in vitro and in vivo, as determined by colony formation, transwell assays and animal experiments. Iso-Seq and RNA-seq data analysis indicated that knockdown of CPSF3 favored use of the distal poly (A) site in the 3'UTR of Cornichon family AMPA receptor auxiliary protein 2 (CNIH2), resulting in a long-3'UTR CNIH2 isoform that produced less CNIH2 protein due to miR-125a-5p targeting and downregulating CNIH2 mRNA through a miR-125a-5p binding site in the long CNIH2 mRNA 3'UTR. Moreover, CPSF3-induced ESCC tumorigenicity was mediated by CNIH2. Taken together, CPSF3 promotes ESCC progression by upregulating CNIH2 expression through loss of miR-125a-5p-mediated CNIH2 repression through alternative splicing and polyadenylation of the CNIH2 mRNA 3'UTR.

Preparation and characterization of astaxanthin-loaded microcapsules stabilized by lecithin-chitosan-alginate interfaces with layer-by-layer assembly method.

Astaxanthin is a kind of keto-carotenes with various health benefits. However, its solubility and chemical stability are poor, which leads to low bio-availability. Microcapsules have been reported to improve the solubility, chemical stability, and bio-availability of lipophilic bioactives. Freeze-dried astaxanthin-loaded microcapsules were prepared by layer-by-layer assembly of tertiary emulsions with maltodextrin as the filling matrix. Tertiary emulsions were fabricated by performing chitosan and sodium alginate electrostatic deposition onto soybean lecithin stabilized emulsions. 0.9 wt% of chitosan solution, 0.3 wt% of sodium alginate solution and 20 wt% of maltodextrin were optimized as the suitable concentrations. The prepared microcapsules were powders with irregular blocky structures. The astaxanthin loading was 0.56 ± 0.05 % and the encapsulation efficiency was >90 %. A slow release of astaxanthin could be observed in microcapsules promoted by the modulating of chitosan, alginate and maltodextrin. In vitro simulated digestion displayed that the microcapsules increased the bio-accessibility of astaxanthin to 69 ± 1 %. Chitosan, alginate and maltodextrin can control the digestion of microcapsules. The coating of chitosan and sodium alginate, and the filling of maltodextrin in microcapsules improved the chemical stability of astaxanthin. The constructed microcapsules were valuable to enrich scientific knowledge about improving the application of functional ingredients.

Circ_0002669 promotes osteosarcoma tumorigenesis through directly binding to MYCBP and sponging miR-889-3p.

Circular RNAs (circRNAs) are a class of highly multifunctional single-stranded RNAs that play crucial roles in cancer progression, including osteosarcoma (OS). Circ_0002669, generated from the dedicator of cytokinesis (DOCK) gene, was highly expressed in OS tissues, and negatively correlated with OS patient survival. Elevated circ_0002669 promoted OS cell growth and invasion in vivo and in vitro. By biotin pulldown and mass spectroscopy, we found that circ_0002669 directly bound to MYCBP, a positive regulator of c-myc, to prevent MYCBP from ubiquitin-mediated proteasome degradation. In addition, circ_0002669 interacted with miR-889-3p and served as a miRNA sponge to increase the expression of MYCBP, as determined by luciferase assays and RNA immunoprecipitation. Functional rescue experiments indicated MYCBP acted as a key factor for circ_0002669- and miR-889-3p-regulated OS cell proliferation and migration. Increased expression of c-myc-associated genes, such as CCND1, c-Jun and CDK4, were found in circ_0002669- and MYCBP-overexpressing OS cells. Our data thus provide evidence that circ_0002669 promotes OS malignancy by protecting MYCBP from protein ubiquitination and degradation and blocking miR-889-3p-mediated inhibition of MYCBP expression.

Fabrication and characterization of dihydromyricetin-loaded microcapsules stabilized by glyceryl monostearate and whey protein-xanthan gum.

Dihydromyricetin (DMY) is a lipophilic nutrient with various potential health benefits; however, its poor storage stability and low solubility and bioavailability limit its applications. This study aims to encapsulate DMY in microcapsules by membrane emulsification and freeze-drying methods to overcome these issues. Glyceryl monostearate (GMS, solid lipid) and octyl and decyl glycerate (ODO, liquid lipid) were applied as the inner cores. Whey protein and xanthan gum (XG) were used as wall materials. The prepared microcapsules had an irregular blocky aggregated structure with rough surfaces. All the microcapsules had a DMY loading of 0.85 %-1.1 % and encapsulation efficiency (EE) >85 %. GMS and XG increased the DMY loading and EE. The addition of GMS and an increased XG concentration led to a decrease in the rehydration rate. The in vitro release and digestion studies revealed that GMS and XG controlled the release and digestion of DMY. The chemical stability results indicated that GMS and XG protected DMY against oxidation. An antioxidant capacity study showed that GMS and XG helped DMY in the microcapsules exert antioxidant effects. This research study provides a platform for designing microcapsules with good stability and high bioavailability to deliver lipophilic bioactive compounds.

Properties of Dietary Flavone Glycosides, Aglycones, and Metabolites on the Catalysis of Human Endoplasmic Reticulum Uridine Diphosphate Glucuronosyltransferase 2B7 (UGT2B7).

Flavone glycosides, their aglycones, and metabolites are the major phytochemicals in dietary intake. However, there are still many unknowns about the cellular utilization and active sites of these natural products. Uridine diphosphate glucuronosyltransferases (UGTs) in the endoplasmic reticulum have gene polymorphism distribution in the population and widely mediate the absorption and metabolism of endogenous and exogenous compounds by catalyzing the covalent addition of glucuronic acid and various lipophilic chemicals. Firstly, we found that rutin, a typical flavone O-glycoside, has a stronger UGT2B7 binding effect than its metabolites. After testing a larger number of flavonoids with different aglycones, their aglycones, and metabolites, we demonstrated that typical dietary flavone O-glycosides generally have high binding affinities towards UGT2B7 protein, but the flavone C-glycosides and the phenolic acid metabolites of flavones had no significant effect on this. With the disposition of 4-methylumbelliferone examined by HPLC assay, we determined that 10 µM rutin and nicotifiorin could significantly inhibit the activity of recombinant UGT2B7 protein, which is stronger than isovitexin, vitexin, 3-hydroxyphenylacetic acid and 3,4-dihydroxyphenylacetic acid. In addition, in vitro experiments showed that in normal and doxorubicin-induced lipid composition, both flavone O-glycosides rutin and flavone C-glycosides isovitexin at 10 µM had no significant effect on the expression of UGT1A1, UGT2B4, UGT2B7, and UGT2B15 genes for 24 h exposure. The obtained results enrich the regulatory properties of dietary flavone glycosides, aglycones, and metabolites towards the catalysis of UGTs and will contribute to the establishment of a precise nutritional intervention system based on lipid bilayers and theories of nutrients on endoplasmic reticulum and mitochondria communication.

An underlying mechanism behind interventional pulmonology techniques for refractory asthma treatment: Neuro-immunity crosstalk.

Asthma is a common disease that seriously threatens public health. With significant developments in bronchoscopy, different interventional pulmonology techniques for refractory asthma treatment have been developed. These technologies achieve therapeutic purposes by targeting diverse aspects of asthma pathophysiology. However, even though these newer techniques have shown appreciable clinical effects, their differences in mechanisms and mutual commonalities still deserve to be carefully explored. Therefore, in this review, we summarized the potential mechanisms of bronchial thermoplasty, targeted lung denervation, and cryoablation, and analyzed the relationship between these different methods. Based on available evidence, we speculated that the main pathway of chronic airway inflammation and other pathophysiologic processes in asthma is sensory nerve-related neurotransmitter release that forms a "neuro-immunity crosstalk" and amplifies airway neurogenic inflammation. The mechanism of completely blocking neuro-immunity crosstalk through dual-ablation of both efferent and afferent fibers may have a leading role in the clinical efficacy of interventional pulmonology in the treatment of asthma and deserves further investigation.

SMART: A Swing-Assisted Multiplexed Analyzer for Point-of-Care Respiratory Tract Infection Testing.

Respiratory tract infections such as the ongoing coronavirus disease 2019 (COVID-19) has seriously threatened public health in the last decades. The experience of fighting against the epidemic highlights the importance of user-friendly and accessible point-of-care systems for nucleic acid (NA) detection. To realize low-cost and multiplexed point-of-care NA detection, a swing-assisted multiplexed analyzer for point-of-care respiratory tract infection testing (SMART) was proposed to detect multiple respiratory tract pathogens using visible loop-mediated isothermal amplification. By performing hand-swing movements to generate acceleration force to distribute samples into reaction chambers, the design of the SMART system was greatly simplified. By using different format of chips and integrating into a suitcase, this system can be applied to on-site multitarget and multi-sample testing. Three targets including the N and Orf genes of SARS-CoV-2 and the internal control were simultaneously analyzed (limit of detection: 2000 copies/mL for raw sample; 200 copies/mL for extracted sample). Twenty-three clinical samples with eight types of respiratory bacteria and twelve COVID-19 clinical samples were successfully detected. These results indicate that the SMART system has the potential to be further developed as a versatile tool in the diagnosis of respiratory tract infection.

MiR-423-5p Inhibition Exerts Protective Effects on Angiotensin II-Induced Cardiomyocyte Hypertrophy.

Angiotensin II (Ang II) is a kind of bioactive peptide, which can contribute to cardiac hypertrophy. MicroRNAs (miRNAs) play critical role in various heart diseases. The cardioprotective effect of miR-423-5p inhibition has been confirmed by previous studies. But its role in cardiac hypertrophy induced by Ang II is unknown. This study focused on the potential of miR-423-5p in cardiomyocyte hypertrophy under the treatment of Ang II. Our results revealed that miR-423-5p expression was upregulated in Ang II-treated human cardiomyocytes (HCMs). Importantly, miR-423-5p knockdown suppressed Ang II-induced cardiomyocyte hypertrophy and oxidative stress in HCMs. Bioinformatics analysis and luciferase reporter assay confirmed that the suppressor of Ty 6 homolog (SUPT6H) was a target gene of miR-423-5p. Interestingly, SUPT6H knockdown aggravated cardiomyocyte hypertrophy and oxidative stress in Ang II-stimulated HCMs, which were then reversed by silenced miR-423-5p. In conclusion, miR-423-5p knockdown exerts its protective effects on Ang II-induced cardiomyocyte hypertrophy in HCMs via modulating SUPT6H expression.

Cardiac MRI Left Atrial Strain Associated With New-Onset Atrial Fibrillation in Patients With ST-Segment Elevation Myocardial Infarction.

BACKGROUND: Left atrial (LA) strain is associated with structural remodeling of the LA. Whether there is an association between LA strain obtained by cardiac magnetic resonance imaging (MRI) and new-onset atrial fibrillation (AF) after ST-segment elevation myocardial infarction (STEMI) is unclear. PURPOSE: To investigate the relationship between LA strain and new-onset AF after STEMI. STUDY TYPE: Retrospective. POPULATION: Three hundred and seventy-nine STEMI patients were enrolled, of which 26 had new-onset AF. FIELD STRENGTH/SEQUENCE: 3.0 T, balanced turbo field echo sequence. ASSESSMENT: Patients were divided into w/o AF group and new-onset AF group. Cardiac MRI images were analyzed using cardiovascular imaging software CVI 42 (Circle Cardiovascular Imaging, Canada). An automatic tracing algorithm was applied to obtain strain values. The reservoir strain, conduit strain, and booster strain were included in model 1, model 2, and model 3, respectively. STATISTICAL TESTS: Student's t-test, Mann-Whiney U test, and chi-square test were performed. Variables with a P ≤ 0.05 were incorporated into the logistic regression analysis. Area under curve of receiver operating characteristic was used to assess the ability of LA strain to identify new-onset AF. Bayesian information criterion, Akaike information criterion, and C-index were used to make comparisons between three models. P < 0.05 was considered statistically significant. RESULTS: Three models were used to assess LA strain identification ability for new-onset AF. After including multiple factors, right coronary artery (RCA), LVEF, and reservoir strain were still risk factors for new-onset AF in model 1. In model 2, age, RCA, LVEF, and conduit strain were still risk factors for new-onset AF. In model 3, RCA, LVEF, LVEDVi, and booster strain were still risk factors for new-onset AF. Model 2 has a stronger identification ability than others. DATA CONCLUSION: LA strain associated with new-onset AF after STEMI. The model including conduit strain was the best-fit one. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY: Stage 3.

Active suspension control with consensus strategy for dynamic posture tracking of wheel-legged robotic systems on uneven surfaces.

This work presents a dynamic posture tracking control strategy for wheel-legged systems on uneven surfaces. Based on the kinematic model of a wheel-legged robotic system, the expected positions for the end-effectors of wheel-legs are calculated according to posture references and sensor feedback. The position control problem for a general wheel-leg is investigated for the active mechanism to imitate a passive suspension and respond to the external contact forces. The position tracking accuracy of the wheel-leg is sacrificed to enhance the compliance performance under rough terrain. Because of the unique contact state with the uneven ground for each wheel-leg, the position responses are different. As a result, the forces from the wheel-legs to the fuselage are inconsistent, which leads to the risk of posture oscillations. Equipping the wheel-legs with an undirected communication network, a consensus scheme for the robotic system is developed with proven global asymptotic stability to improve the posture tracking property. A novel robotic system is established with Stewart-structured wheel-legs, which are connected by a user datagram protocol network. Comparative experimental results are carried out on the physical prototype to validate the effectiveness of the proposed approach.

Association of the serum uric acid to creatinine ratio with metabolic syndrome in the middle age and older population in China.

Background: Metabolic syndrome (MetS) has attracted great interest, with an increasing prevalence. Recent studies have shown that the serum uric acid-to-creatinine ratio (SUACr) might be an excellent biomarker for MetS risk prediction in diabetic patients and postmenopausal women. However, the relationship between SUACr and MetS in a middle-aged and older population remains unclear. Methods: A total of 1277 participants were included in this cross-sectional study. Logistic regression modelling was performed to assess the association between SUACr and MetS in the total population. The dose-response relationship of SUACr and MetS was further assessed by a restricted cubic spline model (RCS). Furthermore, to explore the relationships between the levels of SUACr and the number of metabolic components, analysis of covariance (ANCOVA) was applied. Results: The levels of SUACr were lower in the non-MetS participants (OR 1.60, 95% CI 1.36 to 1.89; P<0.001),. Positive and dose-response relationships were further confirmed by the RCS model. We also found that, with increased number of components, the SUACr tended to increase. Moreover, values of SUACr were strongly related to levels of triglycerides (TGs), body mass index (BMI), blood glucose levels, systolic blood pressure/diastolic blood pressure (SBP/DBP), and hypertension. In addition, the positive association between SUACr and MetS also occurred in those patients with normal uric acid levels. Conclusion: Elevated values of SUACr were strongly associated with an increased risk of MetS; this positive relationship remained in those individuals with normal uric acid levels.

Frequent promoter methylation of HOXD10 in endometrial carcinoma and its pathological significance.

Homeobox D 10 (HOXD10) is important in cell differentiation and morphogenesis and serves as a tumor suppressor gene (TSG) in a number of malignancies. The present study investigated its promoter methylation status and association with the clinicopathological features of endometrial cancer (EC), and measured HOXD10 protein expression levels. EC samples (n=62), including 50 endometroid adenocarcinoma (EA) and 12 mucinous endometrial carcinoma samples (EC) and 70 non-cancerous samples were collected. All samples were evaluated for the methylation status of several TSGs, including HOXD10, using methylation-specific PCR. HOXD10 expression level was evaluated using immunohistochemistry. 5-Aza-2-deoxycytidine treatment was performed in the EC cell line Ishikawa to observe the change in HOXD10 expression levels. HOXD10 promoter methylation was more frequent in cancer samples (P<0.001). Downregulation of HOXD10 in EC samples was confirmed at the protein level using immunohistochemistry (P<0.001) and immunohistochemical staining was negatively associated with methylation status (P<0.05). Less HOXD10 protein was expressed in MEC compared with EA samples (P<0.001). The HOXD10 promoter was hypermethylated in both EA and MEC, causing decreased HOXD10 protein expression levels in EC cells. HOXD10 expression levels were partially reversed by 5-Aza-2-deoxycytidine treatment. The results of the present study demonstrated that epigenetic silencing of HOXD10 putatively contributed to the tumorigenesis of EA. Although there was no significant difference in HOXD10 methylation between EA and MEC, HOXD10 protein expression levels differed between these two diseases, indicating that it may be a useful protein biomarker for distinguishing between these two lesions.

Rapid and efficient isolation and detection of extracellular vesicles from plasma for lung cancer diagnosis.

Extracellular vesicles (EVs) are cell-derived nanoscale vesicles that provide promising biomarkers for the non-invasive diagnosis of cancer because they carry important cancer-related DNA, RNA and protein biomarkers. However, the clinical application of EVs is limited by tedious and non-standardized isolation methods that require bulky instrumentation. Here, we propose an easy-to-operate, simple dielectrophoretic (DEP) method for EV isolation with higher recovery efficiency (>83%) and higher purity than ultracentrifugation (UC). The DEP chip reduces the isolation procedure from 8 h to 30 min. To facilitate subsequent analysis, our DEP chip achieved integration of EV isolation and in situ lysis of EVs for the first time. Our chip also achieved on-chip siRNA delivery to EVs isolated by DEP. We found that EVs isolated from the plasma of lung cancer patients contained higher levels of miR-21, miR-191 and miR-192 compared to those from healthy people. With on-chip detection, EGFR in EVs could distinguish lung cancer patients from healthy people. Overall, this study provides an efficient and practical approach to the isolation and detection of EVs, which could be used for the early diagnosis of lung cancer.

Increased plasma levels of lncRNA H19 and LIPCAR are associated with increased risk of coronary artery disease in a Chinese population.

Recent studies in animal models and humans show that long non-coding RNAs (lncRNAs) are involved in the development of atherosclerosis, which contributes to the pathological foundation of coronary artery disease (CAD). LncRNAs in plasma and serum have been considered as promising novel biomarkers for diagnosis and prognosis of cardiovascular diseases, especially CAD. We here measured the circulating levels of 8 individual lncRNAs which are known to be relevant to atherosclerosis in the plasma samples from 300 patients with CAD and 180 control subjects by using quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) methods. We found that the plasma level of H19 and long intergenic non-coding RNA predicting cardiac remodeling (LIPCAR) were significantly increased in patients with CAD. The area under the receiver operating characteristic curve was 0.631 for H19 and 0.722 for LIPCAR. Multivariate logistic regression analyses indicated that plasma H19 and LIPCAR were independent predictors for CAD, even after adjustment for traditional cardiovascular risk factors. Further studies identified that plasma levels of H19 and LIPCAR were also increased in CAD patients with heart failure compared to those with normal cardiac function. Taken together, our results suggest that increased plasma levels of H19 and LIPCAR are associated with increased risk of CAD and may be considered as novel biomarkers for CAD.

Low-dose green tea intake reduces incidence of atrial fibrillation in a Chinese population.

The aim of the present study was to assessthe association between green tea intake and incidence of atrial fibrillation (AF) in a Chinese population. A total of 801 (mean age: 62 years; 56% male) subjects were enrolled: 401 AF patients and 400 controls. All subjects completed a questionnaire and the associations between their green tea drinking habits and incidence of AF were assessed using the odds ratio (OR) and binary logistic regression. After multivariate adjustment, green tea intake presented as a protective factor against the incidence of AF (OR: 0.349, 95% CI: 0.253-0.483, P < 0.001). The green tea protection showed downward trend with increasing green tea intake (P for the trend= 0.001). Low frequency, low concentration, short-term tea consumption was classified as low-dose green tea intake. Green tea intake decreased the incidence of both paroxysmal AF (OR: 0.307, 95% CI: 0.216-0.436, P < 0.001) and persistent AF (OR: 0.355, 95% CI: 0.261-0.482, P < 0.001) and may be associated with a decreased incidence of AF. This study suggests that low-dose green tea intake strongly protects against AF.

Association of rs10811656 on 9P21.3 with the risk of coronary artery disease in a Chinese population.

BACKGROUND: Genome-wide association studies have reported that the 9p21.3 locus confers risk for coronary artery disease (CAD). However, it is not known whether rs10811656 is linked with CAD in a Chinese population. Thus, the purpose of this study was to investigate the potential association between rs10811656 and the risk of CAD in a Chinese population. METHODS: We conducted a hospital-based, case-control study with 251 CAD patients and 304 controls to examine the potential association of rs10811656 with CAD. RESULTS: The frequencies of the TT genotypes in CAD cases were significantly different from those in controls (adjusted OR: 1.96, 95 % CI: 1.09-3.505, P = 0.024). Compared to controls, rs10811656 was significantly associated with the stable angina pectoris (adjusted OR: 1.42, 95 % CI: 1.06-1.90, P = 0.017), but not with acute coronary syndrome. There was also a highly significant association of rs10811656 with double-vessel and triple-vessel disease when patients were divided into subgroups based on the number of diseased vessels (adjusted OR: 1.68 and 1.60, 95 % CI: 1.14-2.44 and 1.10-2.33, P = 0.009 and 0.02, respectively). CONCLUSION: Our results suggest that the rs10811656 locus might be associated with CAD in a Chinese Han population.

Alcohol consumption and risk of coronary artery disease: A dose-response meta-analysis of prospective studies.

OBJECTIVES: To investigate and quantify the potential dose-response association between alcohol consumption and risk of coronary artery disease (CAD). METHODS: We searched the PubMed database from inception to March 2015 and reviewed the reference list of relevant articles to identify prospective studies assessing the association between alcohol consumption and risk of CAD. Study-specific relative risk (RR) estimates were combined using a random-effects model. Publication bias was estimated using Begg's funnel plot and Egger's regression asymmetry test. The meta-analysis included 18 prospective studies, with a total of 214 340 participants and 7756 CAD cases. The pooled adjusted RRs were 0.62 (95% confidence interval [CI] 0.56-0.68) for highest alcohol consumption amount versus lowest amount. Begg's and Egger's regression tests provided no evidence of substantial publication bias (P = 0.762 for Begg's test and 0.172 for Egger's test). RESULTS: In a dose response analysis, we observed a nonlinear association between alcohol consumption and risk of CAD (P for nonlinearity <0.00). Compared with non-drinkers, the RRs (95% CI) of CAD across levels of alcohol consumption were 0.75 (0.70-0.80) for 12 g/d, 0.70 (0.66-0.75) for 24 g/d, 0.69 (0.64-0.75) for 36 g/d, 0.70 (0.64-0.77) for 60 g/d, 0.74 (0.67-0.83) for 90 g/d, and 0.83 (0.67-1.04) for 135 g/d. CONCLUSIONS: Alcohol consumption in moderation is associated with a reduced risk of CAD with 36 grams/d of alcohol conferring a lower risk than other levels.

Methylation of tumor suppressor gene CDH13 and SHP1 promoters and their epigenetic regulation by the UHRF1/PRMT5 complex in endometrial carcinoma.

OBJECTIVE: Epigenetic changes in cancer and precancerous lesions could be utilized as biomarkers for cancer early detection. This study aims to investigate the novel biomarkers in endometrial carcinoma, and explore their epigenetic regulation. METHODS: Methylation of six tumor suppressor genes (CDH13, SHP1, HIN1, DKK3, CTNNA1 and PCDH8) was evaluated in 155 endometrium samples. Changes of methylation and mRNA expression after treatment with 5-Aza-2'-deoxycytidine (5-Aza-CdR) or/and trichostatin A (TSA) were investigated by MSP and qRT-PCR respectively. Co-immunoprecipitation was used to detect the interactions between UHRF1 and PRMT5 proteins. RESULTS: CDH13 and SHP1 promoters were highly methylated (81.36% and 86.44%, respectively) in endometrial carcinoma, while CDH13 promoter methylation was also present in complex hyperplasia and atypical hyperplasia (51.72% and 50.00%, respectively). Methylation of CDH13 and SHP1 promoters was associated with age and tumor differentiation or muscular infiltration depth. CDH13 and SHP1 promoters were completely methylated in endometrial carcinoma cell lines and were partially reversed by 5-Aza-CdR or TSA to induce mRNA levels (P<0.01). After combined treatment with these two agents, methylation of CDH13 and SHP1 promoters was completely reversed and expression of their mRNA was significantly increased (P<0.01). Moreover, PRMT5 could bind to UHRF1 and down-regulated by 5-Aza-CdR and/or TSA treatment (P<0.05). CONCLUSIONS: Our data demonstrate for the first time that SHP1 methylation has high specificity for diagnosis of endometrial carcinoma, while CDH13 promoter methylation plays a role in the earlier stage. Furthermore, UHRF1 could form a complex with PRMT5 to contribute to the endometrial carcinogenesis.