Systemic lupus erythematosus is an autoimmune disease involving multiple organs of the body. Lupus nephritis is one of the most serious organ manifestations of systemic lupus erythematosus. Vimentin, a member of the intermediate filament protein family, is involved in the pathogenesis of many autoimmune diseases, including lupus nephritis. More and more studies have shown that vimentin plays an important role in the pathogenesis of lupus nephritis, and has an important influence on the disease development, treatment and prognosis of lupus nephritis. This review focuses on the structure, function and post-translational modification of vimentin, the relationship between vimentin and the pathogenesis of lupus nephritis, and the significance of vimentin expression levels in renal tissues, serum and urine, in order to provide theoretical basis for future mechanism research and clinical application.
ObjectiveTo understand research progress of influence of claudins on proliferation and activation for breast cancer. MethodThe relevant literatures of influence of claudins on proliferation and activation for breast cancer were retrieved and reviewed. ResultsThe claudins had 24 members in mammals,claudin-13 was missing in human beings.Expression and distribution mode of the claudins possessed highly tissue-specific,and multiple proteins were expressed in many organizations.The expressions of claudins could be regulated from the levels of transcription and post-transcription,coordinately regulated by the transcription factor and post-synthetic modifications.Claudins were related to epithelial-mesenchymal transition.Now the studies were relatively clear those focused on claudin-1,-2,-4,-6,and other subtypes,and the expression of claudin-1 indicated the poor prognosis of tumor;claudin-2 was closely related to liver metastasis of breast cancer;claudin-4 was closely related to triple negative breast cancer;the function of claudin-6 in the breast cancer was controversial.In addition to the claudins mentioned above,other claudin members also played certain roles in normal breast and malignant breast tumors.Claudin-5 might participate in metastasis of breast cancer through N-WASP and ROCK signal pathway;CD-24 and claudin-7 immunodepression had a certain guiding significance on prognosis of invasive ductal carcinoma;the expressions of claudin-16 and HAPLN3 gene were remarkably increased in human breast cancer;Claudin-20 induced breast cancer cells into a subtype that possessed the high invasiveness and weakened the resis-tance of epithelial-mesenchymal transition.Recently,the claudin-low subtype was proposed,and it differed from other types of breast cancer in many aspects,and also it had a better prognosis than other types of triple negative breast cancer. ConclusionsClaudin,being an important member of tight junction protein,is confirmed to be related to epithelial-mesenchymal transition.Claudins play important roles in dissociaton,activation,invasiveness,and metastasis of breast cancer,but there is no final conclusion which member contributes to invasiveness and metastasis of breast cancer.Moreover,there are opposite conclusions on some certain claudins members in breast cancer which might due to the different subtypes of breast cancer,so,further studies about the function of claudins in different subtypes are needed eagerly.
Objective To study the expression of human Runt-related transcription factor 1 (RUNX1) in rat airway epithelial cells stimulated by cigarette smoking extract (CSE), and explore the role of RUNX1 in regulating epithelial-mesenchymal transition (EMT). Methods Primary rat bronchial epithelial cells were cultured by enzyme digestion and stimulated with different concentrations of CSE. The viability of cells was detected by CCK-8 to explore the appropriate concentration of CSE. After the cells were treated with CSE, the Runx1 interference and overexpression vectors were constructed and transfected into the cells to silence or overexpress the Runx1 gene. Immunocytochemical method was used to detect RUNX1 expression and Western blot analysis was used to detect the expression of RUNX1, nuclear factor-κB (NF-κB), Snail, E-cadherin, and vimentin. Results The survival rate of bronchial epithelial cells could be reduced by CSE, and the degree of reduction was directly positively correlated to the concentration of CSE. After CSE stimulation, the expression level of E-cadherin in primary rat bronchial epithelial cells decreased significantly (P<0.05); the expression levels of RUNX1, NF-κB, Snail and vimentin significantly increased (P<0.05). After interfering with RUNX1 gene, the expression level of E-cadherin was up-regulated (P<0.05), and the expression levels of NF-κB, Snail and vimentin were down-regulated (P<0.05). After overexpression of RUNX1 gene, the expression level of E-cadherin decreased (P<0.05), and the expression levels of NF-κB, Snail and vimentin increased (P<0.05). Conclusions CSE promotes the expression of RUNX1 in rat airway epithelial cells. RUNX1 might regulate EMT process by involving in the regulation of NF-κB /Snail expression.
ObjectiveTo investigate the role of GOLPH3 in esophageal squamous cell carcinoma (ESCC). MethodsWound healing assays, transwell invasion assays and 3D culture were carried out to analyze the cell migration and invasion ability of GOLPH3 overexpression and knockdown KYSE-140 cells. The relationship between GOLPH3 expression and CYR61, CD44 and Snail mRNA expression was further examined through qRT-PCR, to identify the mechanisms involved. ResultsGOLPH3-promoted ESCC cell migration and invasion. CYR61, CD44 and Snail mRNA expression levels were correlated with GOLPH3 protein expression level. ConclusionGOLPH3 overexpression promotes ESCC metastasis through epithelial-mesenchymal transition (EMT), and plays an oncogenesis role in ESCC.
ObjectiveTo summarize the role of epithelial-mesenchymal-transition （EMT） in occurrence and development of gastrointestinal cancer. MethodsDomestic and international publications online involving EMT of gastrointestinal cancer in recent years were collected and reviewed. ResultsEMT was a highly conserved process that has been well characterised in embryogenesis. Studies had shown that the aberrant activation of EMT in adult epithelia could promote tumour metastasis by repressing cell adhesion molecules. E-cadherin， one of the epithelial cell markers, maybe involved in the process of the EMT, especially of the Ecadherin transcriptional repressors， these transcriptional repressors significantly increased in the gastrointestinal cancer. Further more， EMT might involve in the process of gastrointestinal cancer stem cells formation. ConclusionsEMT and it’s regulators play a very important role in gastrointestinal cancer， and may provide a newsight into the gastrointestinal cancer. It also can provide a novel clinical targets to treat the gastrointestinal cancer.
ObjectiveTo investigate the influence of hypoxia on pro-metastasis induced by epithelial-mesenchymal transition (EMT) of human lung adenocarcinoma. MethodsThe human lung cancer cell line H460 was cultured in hypoxic condition and the morphologic changes of the cells were observed under the microscope. The EMT-related markers including E-cadherin and vimentin were detected by Western blot. Transwell migration assay and transwell invasion assay were employed to detect the migratory and invasive activity of cancer cells. ResultsHypoxic induced morphological changes were consistent with the mesenchymal phenotype, such as an elongated fibroblastic morphology, and conversion from a tightly packed epithelial cobblestone pattern to a loosely packed scattered phenotype. Compared with the control group, hypoxic attenuated the quantity of E-cadhenrin, but increased vimentin, which resulted in promotion of migration and invasion of H460. ConclusionHypoxia induces EMT in H460 and enhances the invasive and migratory abilities of lung cancer cells.
Objective To investigate the prognostic value of epithelial-mesenchymal transition （EMT） related proteins （Snail， E-cadherin， and N-cadherin） in gastric cancer and its relationship with tumor initiating cells （TICs） marker （CD133）. Methods The expressions of EMT-related proteins and CD133 protein in the gastric cancer tissues and normal gastric mucosa tissues adjacent to gastric cancer were detected by Western blot method. The relations between the expressions of EMT-related factors proteins and CD133 protein and the clinicopathologic characters were analyzed. The correlations between EMT-related factors and CD133 were analyzed by Spearman. The correlations between EMT-related factors expressions and CD133 expression and survival were analyzed by Kaplan-Meier method and Log-rank test. Results ① The protein expression levels of Snail， N-cadherin， and CD133 in the gastric cancer tissues were significantly higher than those in the normal gastric mucosa tissues adjacent to gastric cancer （Snail：0.599±0.114 versus 0.259±0.108， P=0.020；N-cadherin：0.754±0.154 versus 0.329±0.134， P=0.001；CD133：0.635±0.119 versus 0.485±0.116， P=0.029）， while the protein expression level of E-cadherin was lower than that in the normal gastric mucosa tissues adjacent to gastric cancer （0.378±0.123 versus 0.752±0.156， P=0.003）.② The expression levels of Snail and N-cadherin in the gastric cancer patients with vascular invasion， lymphatic vessel invasion，N3 lymph node metastasis， diameter more than 5 cm， and Ⅲ＋Ⅳ staging were significantly higher than those in the patients without vascular invasion， lymphatic vessel invasion， N0-N2 lymph node metastasis， diameter less than 5 cm， andⅠ＋Ⅱ staging（P＜0.05）， while E-cadherin protein expression was lower than that in the patients without vascular invasion， lymphatic vessel invasion， N0-N2 lymph nodes metastasis， andⅠ＋Ⅱstaging （P＜0.05）. The expression levels of CD133 in the gastric cancer patients with lymphatic vessel invasion， diameter more than 5 cm， and Ⅲ＋Ⅳ staging were significantly higher than those in the patients without lymphatic vessel invasion， diameter less than 5 cm， andⅠ＋Ⅱ staging （P＜0.05）. ③The Snail and N-cadherin protein expressions were significantly positive correlated with CD133 protein expression， respectively （rs=0.278， P=0.048；rs=0.406， P=0.003）， while E-cadherin protein expression was significantly negative correlated with CD133 protein expression （rs=-0.504， P=0.000）.④ The survival time in the patients with lower expressions of Snail， N-cadherin， and CD133 were significantly longer than those in the patients with higher expressions of Snail， N-cadherin， and CD133 （P＜0.05）. The combination of Snail， N-cadherin， E-cadherin， and CD133 could effectively predict survival. Conclusions There is a significant correlation between EMT and gastric cancer TICs， and which are correlated with aggressive clinicopathologic features of gastric cancer. The combination of Snail， E-cadherin， N-cadherin， and CD133 may be effectively predict the prognosis of gastric cancer patients.
Objective To investigate the structure characteristics， functions， and research progress of Notch signaling pathway in digestive tumors. Methods The related literatures about the molecular genetic mechanism of Notch signaling pathway were reviewed. Results The Notch signaling pathway plays an important role not only in normal cells’ growth， differentiation， proliferation， and apoptosis but also in a variety of tumors’ occurrence and development. Conclusion The reasonable regulation to Notch signaling pathway may open up new ways to the treatment of the tumor.
ObjectiveTo explore the effectiveness of Ovol2 gene for epithelial-mesenchymal transition (EMT) to offer some theory evidences for the targeted therapy in lung adenocarcinoma. MethodsA549 cells were treated with control and Ovol2 overexpressioned by lentivirus infection. Real-time PCR were performed to test the mRNA level of genes correlated to EMT. Western Blot was performed for protein level of the following makers:E-cadherin, N-cadherin, vimentin, ect. Moreover, we tested the migration and invasion ability of A549 cells by transwell and wound healing experiment. ResultsAfter treated with Ovol2 overexpressed, the expression level of E-cadherin raised, while the expression level of N-cadherin, vimentin and Twist1 declined in both mRNA and protein expression level. The results of wound healing and transwell experiment indicated that the migration and invasion ability of A549 cells weakened. ConclusionOverexpression of Ovol2 gene can suppress the distant metastasis ability and invasion ability of A549 cells by inhibiting the EMT.
ObjectiveTo explore the role of interleukin-6 (IL-6) in cervical cancer cell C-33A.MethodsThe cervical cancer cells C-33A were divided into the IL-6 group and the control group after culture. The IL-6 group were treated with 50 ng/mL of recombinant IL-6 protein, and the control group were without IL-6. Then cell viability and cell migration were detected by MTT assay and wound-healing assay, respectively. The mRNA and protein expressions of epithelial-cadherin (E-Cad), neural-cadherin (N-Cad), vimentin and transcription factors-snail1 (TFs-SNAIL1) were analyzed by real time quantitative polymerase chain reaction and Western blotting, respectively.ResultsCompared with the control group, in the IL-6 group the proliferation of cervical cancer cells C-33A was promoted (12 h: 0.388±0.025 vs. 0.597±0.057; 24 h: 0.547±0.021 vs. 0.798±0.036; 48 h: 0.745±0.056 vs. 1.296±0.122; 72 h: 1.074±0.053 vs. 1.805±0.113; P<0.05), and the relative migration ability of cervical cancer cell was promoted (12 h: 1.057±0.029vs. 1.200±0.045; 24 h: 1.189±0.036 vs. 1.428±0.181; 48 h: 1.273±0.059 vs. 1.569±0.143; 72 h: 1.409±0.047 vs. 1.623±0.170; P<0.05); meanwhile, compared with the control group, in the IL-6 group, the expression of E-Cad mRNA (1.012±0.098vs. 0.483±0.171, P<0.01) and E-Cad protein (1.032±0.015vs. 0.395±0.119; P<0.01) decreased, the expression of N-Cad mRNA (1.054±0.106vs. 1.465±0.230, P<0.01) and N-Cad protein (1.040±0.043vs. 1.605±0.128, P<0.01) increased, the expression of vimentin mRNA (1.050±0.083vs. 1.340±0.099, P<0.05) and vimentin protein (1.043±0.062vs. 1.430±0.077, P<0.05) increased, and the expression of TFs-SNAIL1 mRNA (1.058±0.176vs. 1.510±0.229, P<0.01) and Fs-SNAIL1 protein (1.022±0.015vs. 1.470±0.139, P<0.01) increased.ConclusionIL-6 may promote the proliferation, migration, and epithelial-mesenchymal transition of cervical cancer cell C-33A.