Analysis of the Runx3 expression during experiemental autoimmune encephalomyelitis

Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system (CNS), which is attributed to a self-sustaining autoimmune mechanism. The majority of the knowledge regarding MS autoagressive mechanisms is resultant of studies performed in its experimental model (mice) the experimental autoimmune encephalomyelitis (EAE).Although, the literature reports that the EAE is mediated by proinflammatory CD4+ T cells , isn’t completely clear how these cells (known as helper cells) would be able of initiate the disease when adoptively transferred to healthy animals.We believe that the Runx3 gene presents a central role in the progression and regulation of the effector activity in CD4+ encephalitogenic lymphocytes.

RUNX3 Epigenetic Inactivation Is Associated With Estrogen Receptor Positive Breast Cancer

The role of Runt-related transcription factor 3 ( RUNX3) gene in breast cancer remains not fully understood. We studied the correlation between RUNX3 gene promoter methylation and estrogen receptor (ER) expression status in breast cancer. Three breast cancer cell lines and 113 formalin-fixed, paraffin-embedded breast cancer tissue samples were analyzed for RUNX3 expression. Methylation-specific polymerase chain reaction was used to analyze RUNX3 methylation on the samples. Migration and invasion ability were evaluated in MCF7 cell line (RUNX3 methylated) treated with methylation inhibitor 5-Aza-2′-deoxycytidine (5-Aza-CdR) to study the effect of RUNX3 methylation status. Our data showed that the expression of RUNX3 was high in MCF10A but not in MCF7 and SKBR3 cell lines, while the RUNX3 promoter showed hypermethylation in MCF7 but not in MCF10A and SKBR3. In tissues samples, Immunohistochemical (IHC) expression of RUNX3 protein was higher in ER-negative samples than in ER-positive cases, and it was negatively correlated with the methylation status of the RUNX3 gene promoter. Proliferation, migration, and invasion of MCF7 were suppressed when 5-Aza-CdR treated. Also, the hypermethylation status of RUNX3 gene promoter was reversed and RUNX3 expression was increased. In summary, our data suggest that hypermethylation of the RUNX3 gene promoter may play an important role in ER-positive breast tumor progression.

Runt-related transcription factor 3 promoter hypermethylation and gastric cancer risk: A meta-analysis

ObjectiveThe aim of this study was to investigate the correlation between runt-related transcription factor 3 (RUNX3) gene promoter hypermethylation and gastric cancer risk by meta-analysis.MethodsBy searching Medline, PubMed, Embase, Cochrane, Ovid and CNKI electronic databases, the open published studies about the association between RUNX3 gene promoter hypermethylation and gastric cancer risk were screened. The hypermethylation rate in cancer tissue and autologous control tissue (normal gastric tissue of gastric cancer patients) were extracted from each included study. The odds ratio (OR) and corresponding 95% confidence interval (95% CI) of RUNX3 gene promoter hypermethylation in cancer tissue versus autologous control tissue of gastric cancer patients were pooled with random or fixed effect models. The publication bias was evaluated by Begg’s funnel plot and Egger’s line regression test.ResultsFinally, twenty three relevant studies were included in this meta-analysis. The hypermethylation rate in cancer tissue and autologous control tissue of gastric cancer patients were 0.56±0.16 and 0.18±0.22 respectively, which demonstrated a hypermethylation rate in cancer tissue significantly higher than that of autologous controls (P<0.05). A significant positive correlation of hypermethylation rate between cancer tissue and autologous control existed for the included 23 studies(rpearson=0.62, P<0.05). For significant heterogeneity across the studies, the OR was pooled by random effects model. The combined OR was 8.06 with the 95% CI of 5.73~11.32, which indicated the hypermethylation frequency in cancer tissue was higher than that of autologous controls.ConclusionThe RUNX3 gene promoter hypermethylation rate was much higher in cancer tissue than that of normal gastric tissue in patients with gastric cancer, which indicates a close association between gastric cancer and RUNX3 gene promoter hypermethylation. Furthermore, RUNX3 gene promoter hypermethylation may be a potential biomarker for gastric cancer diagnosis.

RUNX3 gene in renal cell cancer

Dear Editor, we read the publication on “The expression of RUNX3 gene in renal cell cancer and its clinical relevance with serum vascular endothelial growth factor” with a great interest. Parmar <em>et al</em>. concluded that “Lower expression of RUNX3 in renal cancer suggests its tumor suppressive role”. In fact, the role of RUNX3 is well clarifi d in several malignancies. It is no doubt there is the similar observation for the case of renal cell carcinoma. In the present report, there are some limitations as noted by Parmar <em>et al</em>. An important consideration is the possible concurrent effect of another genetic factor that might modify the fi phenotypic manifestation. In case of RUNX3, the effect of concurrent p53 is well clarifi and should be studied.

The expression of RUNX3 gene in renal cell cancer and its clinical relevance with serum vascular endothelial growth factor

<p>Background: Latest advances indicate that RUNX3 is a candidate tumor suppressor in several types of human cancers, including renal cell cancer.<br />However, its definitive role is not yet established. Vascular endothelial growth factor (VEGF) has been widely studied as a surrogate marker of<br />angiogenic activity and prognostic marker in renal cancer for monitoring treatment response and detection of early relapse. The aim of the study was<br />to examine the clinical significance of RUNX3 expression and serum VEFG in series of renal cancer patients using quantitative real-time polymerase<br />chain reaction and standard enzyme-linked immunosorbent assay kit and find its correlation with renal cancer stage, grade, and histopathology.<br />Materials and Methods: We reviewed our prospectively collected renal cancer database of 47 patients. All patients were evaluated preoperatively<br />and staged and underwent partial or radical nephrectomy as per the feasibility criteria. RUNX 3 expression in tumor tissue and adjoining parenchyma<br />was sampled in all patients, and serum levels of VEGF were measured in pre-and post-operative period on day 7 and day 30 after surgery. 10<br />age- and sex-matched healthy volunteers served as control group. Results: We observed that RUNX3 gene expression was significantly lower in<br />tumor tissue than in normal renal parenchyma of a renal cancer patient. The serum VEGF levels were significantly increased in patients with renal<br />cell carcinoma (RCC) compared to normal healthy volunteers and showed decreasing trend after the surgery. Loss of RUNX3 gene expression<br />and higher VEGF levels strongly correlated with high-grade tumors; however, it was not related to tumor size and histopathology. There was no<br />correlation of RUNX 3 with VEGF levels in RCC patients. Conclusion: The results of this study showed that renal cancer patients had increased<br />VEGF levels which were effectively alleviated by curative resection. Lower expression of RUNX3 in renal cancer suggests its tumor suppressive<br />role and new insights into targeted therapies linking RUNX3 gene may have some diagnostic and therapeutic implications in RCC patients. We did<br />not find any correlation between RUNX3 gene and serum VEGF.</p>