RUNX3 regulates trastuzumab resistance of gastric cancer cells: a metabolomic analysis based on UPLC-Q Exactive Focus Orbitrap mass spectrometry / 南方医科大学学报

OBJECTIVE@#To explore the role of Runt-related transcription factor 3 (RUNX3) in metabolic regulation of trastuzumab-resistant gastric cancer cells and investigate the mechanism of RUNX3 knockdown-mediated reversal of trastuzumab resistance.@*METHODS@#We performed a metabolomic analysis of trastuzumab-resistant gastric cancer cells (NCI N87R) and RUNX3 knockdown cells (NCI N87R/RUNX3) using ultra performance liquid chromatography (UPLC) coupled with Q Exactive Focus Orbitrap mass spectrometry (MS). Multivariate combined with univariate analyses and MS/MS ion spectrums were used to screen the differential variables. MetaboAnalyst 5.0 database was employed for pathway enrichment analysis. Differential metabolites-genes regulatory relationships were constructed based on OmicsNet database. The changes in GSH/GSSG and NADPH/NADP ratios in NCI N87R/RUNX3 cells were measured using detection kits.@*RESULTS@#The metabolic profile of NCI N87R cells was significantly altered after RUNX3 knockdown, with 81 differential metabolites identified to contribute significantly to the classification, among which 43 metabolites were increased and 38 were decreased (P < 0.01). In NCI N87R cells, RUNX3 knockdown resulted in noticeable alterations in 8 pathways involving glutamine metabolism, glycolysis, glycerophospholipid, nicotinate-nicotinamide and glutathione metabolism, causing also significant reduction of intracellular GSH/GSSG and NADPH/NADP ratios (P < 0.01). The differential metabolites-genes network revealed a regulatory relationship between the metabolic molecules and genes.@*CONCLUSION@#RUNX3 reverses trastuzumab resistance in gastric cancer cells by regulating energy metabolism and oxidation-reduction homeostasis and may serve as a potential therapeutic target for trastuzumab-resistant gastric cancer.

Relationship between Expression of Runt-related Transcription Factor 3 and Enhancer of zeste Homolog 2 Proteins and Sensitivity to Neoadjuvant Chemotherapy in Locally Advanced Rectal Cancer / 中国医学科学院学报

Objective To investigate the expression and correlation of Runt-related transcription factor 3(RUNX3)and enhancer of zeste homolog 2(EZH2)in rectal cancer,and to reveal the relationship between the expression of RUNX3 and EZH2 and the sensitivity of XELOX regimen to neoadjuvant chemotherapy in locally advanced rectal cancer patients. Methods The carcinoma and paracancerous tissues of 31 patients with rectal adenocarcinoma and no preoperative antitumor therapy were selected as cancer group and paracancer group,respectively.The relative mRNA levels of RUNX3 and EZH2 in the two groups were measured by real-time quantitative reverse transcription-polymerase chain reaction,and the protein levels were determined by immunohistochemical assay.The expression of RUNX3 and EZH2 was compared between cancer tissue and paracancerous tissue.The pre-treatment wax blocks of 26 patients with locally advanced rectal cancer who received 3 cycles of XELOX regimen as neoadjuvant chemotherapy before surgery were selected as the pre-neoadjuvant therapy group,and the postoperative pathological wax blocks were selected as the post-neoadjuvant treatment group.Tumor regression grade(TRG)was determined to evaluate the efficacy of neoadjuvant therapy.Immunohistochemical assay was used to detect the protein levels of RUNX3 and EZH2 in the two groups,and then the relationship between the expression patterns of the two proteins and the efficacy of neoadjuvant chemotherapy was analyzed. Results Compared with paracancerous tissue,the cancer tissue showed down-regulated mRNA level and reduced positive protein expression rate of RUNX3,while up-regulated mRNA level(

Expression of Runt-related Transcription Factor 3 in Human Colon Cancer Cell Line HCT-116 Resistant to 5-Fluorouracil and the Mechanism of Drug Resistance / 中国医学科学院学报

Objective To establish a human colon cancer cell line HCT-116/5-FU resistant to 5-fluorouracil(5-FU)and explore the relationship between runt-related transcription factor 3(RUNX3)and drug resistance of colorectal cancer.Methods The human colon cancer cell line HCT-116/5-FU with resistance to 5-FU was established by low concentration gradient increment combined with high-dose intermittent shock.CCK-8 method was used to determine the half maximal inhibitory concentration(IC

Regulatory effects of miR-138 and RUNX3 on Th1/Th2 balance in peripheral blood of children with cough variant asthma / 中国当代儿科杂志

OBJECTIVES@#To study the expression levels of microRNA-138 (miR-138) and Runt-related transcription factor 3 (RUNX3) in peripheral blood of children with cough variant asthma (CVA) and their regulatory effects on Th1/Th2 balance.@*METHODS@#Sixty-five children with CVA (CVA group) and 30 healthy children (control group) were enrolled. Peripheral venous blood samples were collected for both groups, and CD4@*RESULTS@#Compared with the control group, the CVA group showed significantly decreased levels of IFN-γ and IL-2 from CD4@*CONCLUSIONS@#MiR-138 regulates Th1/Th2 balance by targeting RUNX3 in children with CVA, providing a new direction for the treatment of CVA.

Expression and clinical significance of runt-related transcription factor 3 in children with bronchiolitis / 中国当代儿科杂志

OBJECTIVE@#To study the mRNA level of runt-related transcription factor 3 (RUNX3) in children with bronchiolitis and its clinical significance in bronchiolitis.@*METHODS@#A total of 54 young children with bronchiolitis were enrolled as the bronchiolitis group, among whom 28 with atopic constitution were enrolled in the atopic bronchiolitis group and 26 with non-atopic constitution were enrolled in the non-atopic bronchiolitis group. A total of 48 healthy young children were enrolled as the healthy control group, among whom 24 with atopic constitution were enrolled in the atopic healthy control group and 24 with non-atopic constitution were enrolled in the non-atopic healthy control group. Quantitative real-time PCR was used to measure the mRNA level of RUNX3 in peripheral blood mononuclear cells. ELISA was used to measure the serum levels of interleukin-4 (IL-4) and interferon gamma (IFN-γ).@*RESULTS@#The bronchiolitis group had a significantly lower mRNA level of RUNX3 than the healthy control group, and the atopic bronchiolitis group had a significantly lower mRNA level of RUNX3 than the non-atopic bronchiolitis, atopic healthy control, and non-atopic healthy control groups (P<0.05). The bronchiolitis group had a significantly higher serum level of IL-4 than the healthy control group, and the atopic bronchiolitis group had a significantly higher serum level of IL-4 than the non-atopic healthy control group (P<0.05). The bronchiolitis group had a significantly lower serum level of IFN-γ than the healthy control group, and the atopic bronchiolitis group had a significantly lower serum level of IFN-γ than the non-atopic bronchiolitis, atopic healthy control, and non-atopic healthy control groups (P<0.05). The correlation analysis showed that the mRNA level of RUNX3 was negatively correlated with the serum level of IL-4 and was positively correlated with the serum level of IFN-γ (P<0.05).@*CONCLUSIONS@#Measurement of RUNX3 gene expression in peripheral blood mononuclear cells has a certain value in identifying children with atopic constitution at high risk of asthma among children with bronchiolitis.

Epigenetic inactivation of RUNX3 in colorectal cancer

PURPOSE: Emerging evidence indicates that runt-related transcription factor 3 (RUNX3) is an important tumor suppressor gene in several cancer types, including colorectal cancer (CRC). However, the clinical significance of RUNX3 inactivation in CRC remains unclear. The aim of this study was to examine the correlation between clinicopathologic factors and RUNX3 hypermethylation/expression in CRC. METHODS: Sixty-two CRC patients who were treated at the Soonchunhyang University College of Medicine were recruited in this study. The hypermethylation of CpG islands in the RUNX3 promoter and the expression of RUNX3 mRNA were identified by methylation-specific polymerase chain reaction (PCR) and reverse transcriptase-PCR, respectively. The expression of RUNX3 was determined by immunohistochemical staining. RESULTS: Of the 62 CRC tissue samples, 20 (32.3%) presented hypermethylated RUNX3 promoters. Aberrant RUNX3 hypermethylation was found to be associated with vascular (P = 0.006) and lymphatic (P = 0.002) invasion. Hypermethylation of RUNX3 was associated with poor survival outcomes (P = 0.038). However, expression of RUNX3 was not a prognostic factor (P = 0.363). CONCLUSION: Hypermethylation of RUNX3 may be a predictor of a poor prognosis in CRC.

RUNX3 Methylation, Loss of RUNX3 Expression and Clinicopathologic Findings according to Helicobacter pylori CagA in Gastric Carcinoma / 대한소화기학회지

BACKGROUND/AIMS: Helicobacter pylori cytotoxin-associated gene A (CagA) has been suggested to be involved in the inactivation of Runt-related transcription factor 3 (RUNX3), a known gastric carcinoma tumor suppressor gene. It remains unclear how H. pylori CagA initiates or maintains RUNX3 promoter methylation and inactivates its protein expression in gastric carcinoma. METHODS: RUNX3 promoter methylation status, RUNX3 expression, and H. pylori CagA were investigated in 76 sample pairs of gastric carcinoma tissue. The patients' medical records were reviewed. The association between RUNX3 methylation or loss of RUNX3 expression and clinicopathologic variables according to H. pylori CagA status were investigated. RESULTS: In gastric carcinoma patients with H. pylori CagA-positive infection, RUNX3 methylation did not show association with lymphatic invasion, venous invasion, and TNM stages. However RUNX3 methylation was observed more frequently in poorly differentiated adenocarcinoma and signet ring cell carcinoma (77.8% vs. 20.0%, p=0.023) in early stage. In gastric carcinoma patients with H. pylori CagA-positive infection, loss of RUNX3 expression did not show association with lymphatic invasion, venous invasion, and TNM stages. However loss of RUNX3 expression was observed more frequently in early gastric carcinoma than in advanced gastric carcinoma (84.2% vs. 75.0%, p=0.51), but this difference was not significant. CONCLUSIONS: In gastric carcinoma patients with H. pylori CagA-positive infection, RUNX3 methylation or loss of RUNX3 expression did not show correlation with lymphovascular invasion and TNM stages. In early gastric carcinoma patients with H. pylori CagA-positive infection, RUNX3 methylation was observed more in poorly differentiated adenocarcinoma and signet ring cell carcinoma.

Correlation between the methylation status of Runx3 gene and positive expression of estrogen receptor in breast cancer / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the relationship between hypermethylation of Runx3 gene promoter and estrogen receptor (ER) and the implications of Runx3 gene promoter hypermethylation in ER positive breast cancer.</p><p><b>METHODS</b>Western blot and RT-PCR were used to detect the protein and mRNA expression of Runx3 gene in breast cancer cell lines (MCF7 and SKBR3) and normal breast epithelium cell line (MCF10A). Immunohistochemical SP method was used to detect the expression of ER and Runx3 proteins in 113 tissue samples of breast cancer. Moreover, methylation specific PCR was used to detect RUN3 promoter methylation in cell lines MCF7, SKBR3, MCF10A and 113 tissue samples of breast cancer.</p><p><b>RESULTS</b>Of the 3 cell lines, Runx3 protein and mRNA were detectable in MCF10A, but were absent in MCF7 and SKBR3. MCF7 had a high methylation status at Runx3 promoter, in contrast, MCF10A and SKBR3 showed unmethylated RUN3 promoter. Among the 113 cases of breast cancer, 68 cases were ER positive and 45 were negative. The positive rates of Runx3 protein expression in ER positive and negative tumors were 26.5% (18/68) and 66.7% (30/45), respectively (P<0.05). Runx3 promoter hypermethylation was seen in 82.4% (56/68) of ER positive breast cancer cases and 22.2% (10/45) of ER negative ones (P<0.05). Among 68 cases of ER positive cases, Runx3 promoter hypermethylation was positively correlated with the clinical tumor stage (OR=5.84, P<0.05).</p><p><b>CONCLUSIONS</b>Runx3 gene promoter hypermethylation is present mainly in the ER positive breast cancers. Testing of Runx3 promoter methylation may provide additional reference for clinical stage and prognosis of breast cancer patients, especially in those with ER positive tumors.</p>

Methylation of Runx3 promoter in different breast lesions / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the methylation status of Runx3 promoter and Runx3 expression in breast lesion tissues.</p><p><b>METHODS</b>One hundred and fourteen breast lesions, including 35 cases of fibroadenoma, 39 cases of intraductal carcinoma, 40 cases of invasive ductal carcinoma, and 33 cases of normal breast tissue from Fabruary 2010 to August 2012 were included in this study. Runx3 protein expression was assessed by immunohistochemical SP method; whereas methylation of Runx3 promoter was assessed by high resolution melting (HRM) analysis.</p><p><b>RESULTS</b>Runx3 protein was mainly expressed in the cytoplasm of ductal epithelial cells. The expression rates of Runx3 in normal breast tissue, fibroadenoma, ductal carcinoma in situ, invasive ductal carcinoma were 87.9% (29/33), 85.7% (30/35), 53.8% (21/39), and 40.0% (16/40) respectively. The methylation rates of Runx3 promoter were 12.1% (4/33), 20.0% (7/35), 46.2% (18/39), and 57.5% (23/40), respectively. Correlation analysis between promoter methylation and protein expression of Runx3 in different breast tissue showed the r value in normal breast tissue, fibroadenoma, ductal carcinoma in situ and invasive ductal carcinoma was -0.431 (P = 0.012), -0.408 (P = 0.015), -0.589 (P = 0.000) and -0.743 (P = 0.000) respectively.</p><p><b>CONCLUSIONS</b>Runx3 protein expression shows a downward trend in ductal carcinoma in situ and invasive ductal carcinoma, meanwhile its promoter methylation increases significantly. The methylation of Runx3 promoter may be one of the important factors in the occurrence and development of breast cancer.</p>

Expression of Runx3 and C-myc in human colorectal cancer / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate Runx3 and C-myc expressions in colorectal cancer and their relationship with the clinicopathological parameters.</p><p><b>METHODS</b>Real-time quantitative PCR was used to detect Runx3 and C-myc mRNA expressions in 38 colorectal cancer tissues and matched adjacent tissues, and Runx3 and C-myc expressions was detected by Western blotting in 63 pairs of colorectal cancer and adjacent tissues. The results were stratified according to the clinicopathological characteristics to examine the relationship of Runx3 and C-myc expressions with the clinicopathological factors in the patients.</p><p><b>RESULTS</b>Runx3 expression was down-regulated and C-myc expression up-regulated at both mRNA and protein levels in colorectal cancer tissues compared with the normal tissues, and their protein expressions exhibited an inverse correlation (r=-0.398, P=0.001). Runx3 and C-myc expressions differed significantly between tumors with different Dukes stages, depths of tumor invasion, lymph node statuses, or histological differentiation (P<0.05); Runx3 down-regulation and C-myc up-regulation were more obvious in tumors in advanced Dukes stage and in poorly differentiated tumors.</p><p><b>CONCLUSION</b>Abnormal expressions in Runx3 and C-myc may contribute to the occurrence and development of colorectal cancer and are closed correlated with the patient's clinicopathological parameters.</p>

Relationship between promoter methylation of Syk and Runx3 genes and postoperative recurrence and metastasis in gastric carcinoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the relationship between aberrant methylation of Syk and Runx3 genes and recurrence and metastasis after resection of gastric cancer.</p><p><b>METHODS</b>Applying methylation-specific polymerase chain reaction technique, promoter methylation of Syk and Runx3 genes in the tumor tissues and adjacent normal tissues of gastric cancer patients were detected to investigate the relationship between methylation status of the promoter region of Syk and Runx3 genes and postoperative recurrence and metastasis.</p><p><b>RESULTS</b>In the 70 cases of gastric cancer, the frequencies of promoter methylation of Syk and Runx3 genes were 45.7% (32/70) and 55.7% (39/70) in gastric cancer, and 0 (0/70) and 7.1% (5/70), respectively, in the adjacent normal tissues. The rates of promoter methylation of Syk and Runx3 genes in the gastric cancers were significantly higher than that in the adjacent normal tissues (P < 0.001 for all). The promoter methylation of Syk and Runx3 genes was significantly correlated with the degree of tumor differentiation, depth of invasion, lymph node metastasis and pathological staging (P < 0.05 for all). The frequency of postoperative recurrence and metastasis in 32 patients with Syk promoter methylation was 65.6% (21/32) and that in 38 cases with Syk promoter unmethylation was 18.4% (7/38), showing a significant difference between the two subgroups (χ(2) = 16.13, P < 0.001). The rate of postoperative recurrence and metastasis in 39 patients with Runx3 promoter methylation was 61.5% (24/39) and that in 31 patients with Runx3 promoter unmethylation was 12.9% (4/31, P < 0.001).</p><p><b>CONCLUSIONS</b>The methylation of Syk and Runx3 promoters plays an important role in postoperative recurrence and metastasis of gastric cancer. Combined detection of promoter methylation of Syk and Runx3 genes is helpful for early diagnosis and evaluation of prognosis of gastric cancer.</p>

An Inverse Relationship between the Expression of the Gastric Tumor Suppressor RUNX3 and Infection with Helicobacter pylori in Gastric Epithelial Dysplasia

BACKGROUND/AIMS: This study was performed to determine the association between RUNX3 expression and Helicobacter pylori infection in premalignant gastric lesions. METHODS: We examined 107 patients with gastric epithelial dysplasia who had undergone endoscopic mucosal resection or submucosal dissection. All tissue samples were evaluated by RUNX3 staining and subclassified by immunophenotype. H. pylori infection in dysplastic lesions and the normal surrounding tissue was examined by silver staining, and cagA status was assessed by polymerase chain reaction. RESULTS: The loss of RUNX3 expression was observed in 62 cases (57.9%), and an association with H. pylori infection was found in 54 cases (50.5%). The infection rate with the cagA-positive H. pylori strain was 63.0%. In RUNX3-negative lesions, the rate of H. pylori infection (p=0.03) and the frequency of category 4 lesions (according to the revised Vienna classification) were high (p=0.02). In addition, the gastric mucin phenotype was predominant. In RUNX3-negative category 4 lesions, the rate of cagA-positive H. pylori infection rate was high but not significantly increased (p=0.08). CONCLUSIONS: Infection with H. pylori is associated with inactivation of RUNX3 in early gastric carcinogenesis. This mechanism was prominent in gastric cancer with a gastric mucin phenotype.

Effect of 5-aza-2'-deoxycytidine on growth and methylation of RUNX3 gene in human pancreatic cancer cell line MiaPaca2 / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the effect of demethylating agent 5-aza-2'-deoxycytidine (5-Aza-CdR) on the growth of human pancreatic cancer cell line MiaPaca2 and the expression and methylation of tumor suppressor gene RUNX3.</p><p><b>METHODS</b>Human pancreatic cancer cell line MiaPaca2 cells were treated with different concentrations of 5-Aza-CdR. Morphological changes of MiaPaca2 cells were observed by light microscopy. The activity of cell proliferation was analyzed by MTT assay. The changes of RUNX3 mRNA expression were detected by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR). Changes of RUNX3 gene methylation was detected by methylation-specific polymerase chain reaction.</p><p><b>RESULTS</b>MiaPaca2 cells were treated with 2.5, 5, 10 and 20 µmo1/L 5-Aza-CdR, respectively. The inhibition rates of MiaPaca2 cells treated for 24 h were (9.17 ± 2.15)%, (10.75 ± 2.04)%, (12.57 ± 1.64)% and (18.70 ± 1.51)%, respectively. The inhibition rates were (14.94 ± 1.68)%, (18.60 ± 1.57)%, (22.84 ± 1.58)% and (33.24 ± 1.53)%, respectively, after 48 h treatment; (21.46 ± 1.60)%, (28.62 ± 1.72)%, (35.14 ± 1.64)% and (45.06 ± 1.47)%, respectively, after 72 h treatment; and (26.35 ± 1.71)%, (34.48 ± 1.69)%, (40.05 ± 1.60)% and (49.99 ± 1.61)%, respectively, after 96 h treatment. The differences between inhibition rates of each experimental and control groups (0.00 ± 0.00)% were statistically significant (P < 0.05). At the same time, the inhibition rates of different concentration groups showed significant differences (P < 0.05). At 48 h, 72 h and 96 h, the inhibition rates of each pair concentration groups showed significant differences (P < 0.05). 5-Aza- CdR inhibited the growth of MiaPaca2 cells, and the higher the concentration, the stronger the inhibition after 24 h. 5-Aza-CdR also reversed the methylation status of RUNX3 gene, and restored the expression of RUNX3 mRNA with a dose-effect relationship.</p><p><b>CONCLUSIONS</b>The methylation of RUNX3 gene is significantly related with the occurrence and development of pancreatic cancer, and abnormal methylation of RUNX3 gene may contribute to the loss of RUNX3 mRNA expression. 5-Aza-CdR may effectively cause reversion of RUNX3 methylation, and treatment with 5-Aza-CdR can reactivate the gene expression and inhibit the cell growth. This may provide a new way for diagnosis and treatment of pancreatic cancer.</p>

Correlation of CpG methylation status of Runx3 with pathogenesis of gastric carcinoma / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the role of Runx3 gene CpG island methylation in the development of human gastric carcinoma.</p><p><b>METHODS</b>A total of 150 tumor specimens from patients with gastric carcinoma and 50 normal tissue specimens were selected. Methylation specific PCR (MSP) and pyrosequencing (PS) were used to detect the methylation status of Runx3 gene promoter.</p><p><b>RESULTS</b>Compared to normal tissue samples, a significant increase of CpG island methylation status of Runx3 gene was observed in gastric carcinomas (MSP: 67.3% vs. 40.0%, P = 0.002; PS: 76.0% vs. 30.0%, P < 0.01). Runx3 gene methylation was only related to tumor size (P < 0.05) based on MSP analysis. PS test however showed that the extent of methylation of Runx3 gene was related to the tumor size (P = 0.004), Lauren's classification (P = 0.043), depth of invasion (P < 0.01), lymph node metastasis (P = 0.021) and TNM staging (P = 0.045).</p><p><b>CONCLUSIONS</b>Methylation status of Runx3 gene detectable by PS is closely correlated with clinicopathological parameters of gastric carcinoma, including tumor size, Lauren's classification, depth of invasion, lymph node metastasis and TNM staging. PS is more sensitive than MSP in the detection of Runx3 gene methylation, which may serve as an important marker for early diagnosis and treatment of gastric carcinoma.</p>

Epigenetic Regulation of RUNX3 in Thyroid Carcinoma

No abstract available.

DNA Methylation of RUNX3 in Papillary Thyroid Cancer

BACKGROUND/AIMS: The relationship between Runt-related transcription factor 3 (RUNX3) gene inactivation and various solid tumors has been reported; however, little information is available about RUNX3 in thyroid cancers. METHODS: We evaluated the DNA methylation of RUNX3 in 13 papillary thyroid cancer tissues and four thyroid cancer cell lines. Additionally, using reverse transcriptase-polymerase chain reaction, we analyzed RUNX3 gene expression in several thyroid cancer cell lines after treating with the demethylating agent 5-aza-2'-deoxycytidine (DAC). RESULTS: RUNX3 was hypermethylated in many thyroid cancer cell lines and in 10 of the 12 papillary thyroid cancer tissues. Treatment with DAC increased the expression of RUNX3 in some thyroid cancer cell lines. CONCLUSIONS: We suggest that RUNX3 is associated with thyroid carcinogenesis, and RUNX3 methylation is a potentially useful diagnostic marker for papillary thyroid cancer.

RUNX3 promoter hypermethylation and prognosis of early surgically resected non-small cell lung cancers / 中南大学学报(医学版)

OBJECTIVE@#To determine the relation between the promoter methylation status of RUNX3 gene and clinicopathological parameters, prognosis of non-small cell lung cancer (NSCLC).@*METHODS@#We collected 80 formalin-fixed paraffin-embedded lung cancer tissue samples from NSCLC patients who received postoperative adjuvant chemotherapy with cisplatin. Genomic DNA was extracted through phenol/chloroform extraction. The methylation status of RUNX3 was determined by nested methylation-specific PCR (nMSP). We investigated the pathological and prognostic characteristics of NSCLC stratified by methylation status.@*RESULTS@#The RUNX3 promoter methylation was observed in 20 of the 80 NSCLC samples (25.0%). Methylation of RUNX3 was more frequent in adenocarcinomas (36%) than in squamous cell carcinomas (11%) (P=0.020). In multivariate Logistic regression, positive RUNX3 methylation status (P=0.011) was found to be independent disease-free survival factor as was N stage (P<0.001). Kaplan-Meier curves showed patients with RUNX3 methylation had a significantly poorer overall survival than those without methylation (P=0.003; log-rank test). In multivariate Cox proportional hazards regression analysis, RUNX3 methylation (RR:2.345, 95% CI:1.30-4.865, P=0.022) was a significant independent prognostic factor for the overall survival.@*CONCLUSION@#RUNX3 methylation is a significant independent prognostic factor for disease-free survival and overall survival.

Expression of RUNX3 in cervical carcinoma and its clinical significance / 中南大学学报(医学版)

OBJECTIVE To explore the role of runt-related transcription factor 3(RUNX3) in the tumorgenesis and progression of cervical carcinoma. METHODS The immunohistochemical staining technique was used to detect the expression of RUNX3 protein in 25 cases of normal cervix, 34 intraepithelia neoplasia (CIN), and 48 cervical carcinomas. SYBR Green I chimeric fluorescence Real-time PCR was applied to detect the expression of RUNX3 mRNA in 10 cases of normal cervix, 24 CIN, and 30 cervical carcinomas. RESULTS The expressions of RUNX3 protein and mRNA in normal cervix, CINI,CINII-III, and cervical carcinoma tissues tended to be down-regulated. There was significant difference among these groups (P 0.05). CONCLUSION RUNX3 may function as a tumor suppressor gene in the occurrence and progression of cervical carcinoma.

Colonic expression of Runx3 protein and TGF-β(1) and their correlation in patients with irritable bowel syndrome

OBJECTIVE@#To investigate the role of Runx3 protein and TGF-β(1) in the pathogenesis of irritable bowel syndrome (IBS), as well as the correlation of these two proteins.@*METHODS@#Colonic tissue was collected from patients with IBS and normal persons. The colonic expression of Runx3 protein and TGF-β(1) was detected with immunohistochemistry method. Semi-quantitative analysis was used to evaluate the staining degree of these two proteins.@*RESULTS@#Compared with their counterparts, patients with IBS did not show any changes in the colonic expression of Runx3 protein and TGF-β(1) (P>0.05). Interestingly, there was a significant correlation between Runx3 protein and TGF-β(1) in patients with IBS(P<0.05).@*CONCLUSIONS@#The role of Runx3 protein and TGF-β(1) in the pathogenesis of IBS remains to be further studied.

Study on the expression of Runx3 and TGF-β₁ protein in the colonic tissue from rats with irritable bowel syndrome

OBJECTIVE@#To investigate the expression of Runx3 and TGF-β(1) protein in the colon from rats with irritable bowel syndrome (IBS).@*METHODS@#Rat model for IBS was established by intracolonic instillation with acetic acid and restraint stress methods, which was confirmed by determinating the visceral sensitivity of the animals, including abdominal withdrawal reflex (AWR) score and the electronic behavior of the abdomen wall. The rats were randomly assigned into three groups: IBS(1) group (restraint stress, n = 25); IBS(2) group (both instillation with acetic acid and restraint stress, n = 25) and Control group (n=16). The colonic tissue samples were collected for histological study and the expression of Runx3 and TGF-β(1) proteins were detected by immunohistochemistry. Meanwhile, the relationship of these two proteins was calculated.@*RESULTS@#Visceral hypersensitivity (AWR and abdominal electrical activity) was significantly enhanced in IBS(1) and IBS(2) groups than other groups. The colon tissue in all groups did not show any signs of inflammation. Furthermore, the expression of Runx3 and TGF-β(1) protein in the colon from all groups show no significant difference (P>0.05), with no remarkable relevancy between each other (P>0.05).@*CONCLUSIONS@#The rat model for IBS was successfully established. We did not find any significant changes in the expression of Runx3 and TGF-β(1) protein in the colon tissue from IBS rats, suggesting that the quantitative changes may be not the way by which Runx3 and TGF-β(1) protein play their roles in IBS. The accurate roles of Runx3 and TGF-β(1) proteins in the pathogenesis of IBS remains to be further studied.