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Objective:To study the clinical value of SRY-Box transcription factor 7 ( SOX7) gene methylation in renal cancer and its effect on the biological behavior of renal cancer cells. Methods:80 patients with renal cancer (the kidney cancer group) and 50 patients with benign renal disease (the control group) were selected as the research subjects. Synthetic oligonucleotide sequences (MON, UMON, and CON) were designed and transfected into A498 renal carcinoma cells. Methyl-specific PCR was used to detect the methylation status of the SOX7 gene in the tumor and adjacent tissue of the kidney cancer group as well as in the renal tissue of the control group. The relationship between SOX7 gene methylation and clinicopathological factors was analyzed. The migration and invasion of A498 renal cancer cells in the MON group, UMON group, and CON group were detected by the Transwell chamber. Results:The SOX7 gene methylation rate in tumor tissue of the kidney cancer group was significantly higher than that of the control group and the adjacent tissue, and the difference was statistically significant (χ 2 = 67.522, P < 0.05). The SOX7 gene is methylated in renal cancer cell lines such as Caki-1, 786-O, 769-P, while it is unmethylated in A498 renal cancer cells. There were no statistical differences in the SOX7 gene methylation rate in the tumor tissue of the renal cancer group in terms of gender, age, or pathological type (all P > 0.05). There were statistical differences in the degree of differentiation, maximum tumor diameter, lymph node metastasis, tumor number, and TNM staging in the renal cancer group in terms of tumor tissue SOX7 gene methylation rate (all P < 0.05). After transfection with MON, the SOX7 gene methylation of A498 renal cancer cells could be successfully induced, and the day-1 to day-7 cell viability, cell migration, and invasion numbers of A498 renal cancer cells in the MON group were significantly higher than those in the UMON group and the CON group ( P < 0.05). Conclusions:Hypermethylation of the SOX7 gene can promote the proliferation, migration, and invasion of renal cancer cells and has important clinical value in the evaluation of the disease and prognosis of renal cancer.
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AIM: To investigate the effect of lncRNA MALAT1 on the proliferation, migration and angiogenesis of retinal vascular endothelial cells and its molecular mechanism.METHODS: The expression levels of lncRNA MALAT1 in plasma of normal control group, diabetic without retinopathy group and diabetic retinopathy group were detected by qPCR and the effect of glucose culture on the expression levels of lncRNA MALAT1 were detected by qPCR too. The expression level of miR-124-3p was detected by qRT-PCR; Western blotting was used to detect the expression level of SOX7; The targeting relationship between lncRNA MALAT1 and miR-124-3p, miR-124-3p and SOX7 were detected by the dual-luciferase reporter system; CCK-8 assay was used to detect cell proliferation activity; Transwell assay was used to detect the migration ability of cells; Angiogenesis of hRMECs cells was measured by in vitro tube formation assay.RESULTS:The expression level of lncRNA MALAT1 in plasma of diabetic retinopathy patients was significantly higher than that of diabetic without retinopathy group and normal control group(P<0.001). In vitro glucose culture significantly promoted the expression of lncRNA MALAT1 in hRMECs cells, as well as the proliferation, migration and angiogenesis of hRMECs cells(all P<0.05). Knockdown of lncRNA MALAT1 significantly inhibited the proliferation, migration and tubule formation of hRMECs cells(all P<0.05). Dual-luciferase reporter gene assay showed that lncRNA MALAT1 targeted with miR-124-3p, and miR-124-3p targeted with SOX7. Overexpression of miR-124-3p significantly inhibited the proliferation, migration and tubule formation of hRMECs cells(all P<0.05). Overexpression of lncRNA MALAT1+miR-124-3p, miR-124-3p+SOX7, and knockdown of lncRNA MALAT1+overexpression of SOX7 all significantly eliminated the inhibitory effect of hRMECs cells(all P<0.05).CONCLUSION: lncRNA MALAT1 promote the proliferation, migration and angiogenesis of retinal endothelial cells in diabetic retinopathy by down-regulating the negative regulation of miR-124-3p on SOX7. Therefore, abnormal upregulation of lncRNA MALAT1 in patients with diabetic retinopathy is a potential biomarker.
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Objective The SOX7 gene plays a tumor-suppressive role in a variety of tumors, but there are few reports on whether it plays a role in bladder cancer. This study aims to investigate the expression of SOX7 gene in bladder cancer as well as to investigate the regulation and significance of SOX7 promoter methylation on bladder cancer. Methods GEPIA, Oncomine, MethHC, and cBioPortal databases were used to speculate the SOX7 expression and promoter methylation in bladder cancer tissues. 40 urine samples were collected from January 2017 to October 2017 in the Department of Urology, Tenth People's Hospital of Shanghai City, including 20 samples from bladder cancer patients and the rest 20 from regular patients as a control group. The methylation difference of SOX7 gene was detected by methylation-specific PCR. The bladder cancer cell line was cultured. The medium containing the methylated drug 5-aza-2’ deoxycytidine (5-aza-dc) was added to the Taza cells as the 5-aza-dc group, while T24 cells were added the same volume of DMSO as the control group. The bladder cancer cell line was transfected with the SOX7 plasmid as the plasmid group, and the transfected with the unloaded plasmid was the empty group. Western blot was used to detect the expression of SOX7 in bladder cancer cell lines, and the proliferation, clone formation, and apoptosis of bladder cancer cells after demethylation were detected by CCK-8 experiments, plate cloning experiments, and flow cytometry, respectively. Results The level of methylation in bladder cancer was significantly higher than that in healthy tissues (P<0.005). The higher levels of SOX7 methylation were observed in the urine of 15 bladder cancer patients (75%), compared with only 7 patients (35%) in normal urine, and the proportion was statistically different (P<0.05). The expression of SOX7 protein in the 5-aza-dc group was up-regulated compared to the control group. The expression of SOX7 protein was relatively high when the concentration reached 20 μmol/L. The expression of SOX7 protein in the plasmid group was significantly higher than that in the unloaded group. CCK-8 results showed that the A value of the 5-aza-dc group was statistically lower than that of the control group on the fifth day (P<0.05), and the A value of T24 cells in the plasmid group was significantly lower than that in the unloaded group. The colony formation experiment showed that the number of colony formation per well in the 5-aza-dc group (167.33 ± 13.65) was significantly lower than that in the control group (328.00 ± 20.81) (P<0.05). The number of clone formation per well in the plasmid group (136.00 ± 15.00) was significantly lower than that in the unloaded group (280.67 ± 13.43) (P<0.05). The apoptosis rate of T24 cells in the 5-aza-dc group (27.89%) was significantly higher than that of the control group (3.79%) (P<0.05), and the apoptosis rate of the plasmid group (21.28%) was higher than that of the no-load group (9.90%). Conclusion SOX7 is lowly expressed in bladder cancer, which is regulated by promoter methylation. It is a potential biological marker of bladder cancer and plays a vital role in the occurrence and development of bladder cancer.
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Glioma is a common malignant tumor of nervous system.Many genes of SOX family are closely related to the genesis and development of glioma,among which SOX2,SOX4,SOX7,SOX9 gene are all abnormal in glioma.SOX2 gene is highly expressed in glioma and has positive correlation with the malignant grade of glioma.SOX2 gene coordinates with many factors and promotes the genesis and development of glioma.SOX4 gene plays as both a oncogene and a tumor suppressor gene in brain glioma,and can regulate a variety of factors.SOX7,as a tumor suppressor gene,shows low expression in glioma,and suppresses the genesis of brain glioma by regulating the related factors and signaling pathways.SOX9 gene is highly expressed in glioma tissues,and promotes tumorigenesis and metastasis of glioma by coordinating with a variety of factors,and can be used as an important risk factor for the prognosis of glioma patients.
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Glioma is a common malignant tumor of nervous system.Many genes of SOX family are closely related to the genesis and development of glioma,among which SOX2,SOX4,SOX7,SOX9 gene are all abnormal in glioma.SOX2 gene is highly expressed in glioma and has positive correlation with the malignant grade of glioma.SOX2 gene coordinates with many factors and promotes the genesis and development of glioma.SOX4 gene plays as both a oncogene and a tumor suppressor gene in brain glioma,and can regulate a variety of factors.SOX7,as a tumor suppressor gene,shows low expression in glioma,and suppresses the genesis of brain glioma by regulating the related factors and signaling pathways.SOX9 gene is highly expressed in glioma tissues,and promotes tumorigenesis and metastasis of glioma by coordinating with a variety of factors,and can be used as an important risk factor for the prognosis of glioma patients.
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SOX7 belongs to the SOX gene family.And it has been shown to regulate multiple biological processes.Studies have found that SOX7 gene is likely to be a tumor suppressor gene.In many tumors,SOX7 downregulation that inhibits proliferation,migration and invation of tumor via regulating the Wnt-β-catenin signaling pathway mediated the transcription process,which plays a significant role in tumorigenesis.
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Sox gene family is composed of a class of SRY gene,encoding a series of transcription factors.In the ontogeny,sox genes involved in a variety of development,such as sex determination and differentiation,neural development,cartilage formation.In recent years,researchers found that the abnormal expression of sox gene was related with the development of breast cancer,such as,the overexpression of Sox2 and Sox4 was related with breast cancer; Sox7 and Sox17 in breast cancer could act as tumor suppressor gene,the downregulation of which could activate Wnt/β-catenin signaling pathway.
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Objective This study aimed to investigate the expression of SOX7,β-catenin and cyclin D1 in invasive breast cancer and hyperplastic disease of the breast,and explore their relationship with clinical pathology charactersis in invasive breast cancer in order to provide valuable biomarkers for the treatment and prognosis.Methods The expression of SOX7,β-catenin and cyclin D1 was neasured in 50 invasive breast cancer tissues and 30 hyperplastic disease of the breast by immunohistochemical SP method.The correlations of SOX7,β-catenin and cyclin D1 in invasive breast cancer to clinicopathologic features were analyzed,such as age,size of tumor,axillary lymph node metastasis,histological grade,pTNM stage,ER,PR,Her-2 expression and the risk.Results Immunohistochemical results showed that the positive rates of SOX7 and cyclin D1 in invasive breast cancer were 42％ (21/50)and 70％ (35/50),and the abnormal expression rates of β-catenin in invasive breast cancer was 70％ (35/50).The positive rates of SOX7 in invasive breast cancer was significantly lower than that in hyperplastic disease of the breast 70％ (21/30).The expression of SOX7 had difference between two groups (P =0.021 ＜0.05).The abnormal expression rates of β-catenin and the positive rates of cyclin D1 in invasive breast cancer wcre significantly higher than that in hyperplastic disease of the breast 43.3％ (13/30) (P =0.033 ＜ 0.05) and 20％ (6/30) (P =0.000 ＜ 0.001).The expression of β-catenin and cyclin D1 had difference between two groups.In invasive breast cancer,SOX7 and β-catenin protein expression in 12 cases,while negative expression in 5 cases; SOX7 and cyclin D1 protein positive expression in H 1 cases,while negative expression in 5 cases; β-catenin and cyclin D1 protein positive expression iu 28 cases,while negative expression in 8 cases.Results of the analysis by Spearman showed that in invasive breast cancer the SOX7 protein expression was negatively correlated with the abnormal expression of β-catenin protein and the expression of cyclin D1 protein(r =-0.282,P =0.046 ＜ 0.05 ;r =-0.327,P =0.020 ＜ 0.05)while the abnormal expression of β-catenin protein was positively correlated with the expression of eyclin D1 protein(r =0.333,P =0.018 ＜ 0.05).In invasive breast cancer the expression of SOX7 protein was correlated with age,axillary lymph node metastasis,histological grade,pTNM stage,ER,PR,Her-2 expression and the risk(P ＜0.05),but with no correlation with size of tumor (P ＞ 0.05).However,the abnoral expression of β-catenin and the positive expression of cyclin D1 in invasive breast cancer were correlated with size of tumor,axillary lymph node metastasis and pTNM stage(P ＜ 0.05),but with no correlation with age,histological grade,ER,PR,Her-2 and the risk(P ＞0.05).Conclusions SOX7.β-catenin and cyclin D1 are frequently abnormality-regulated in invasive breast cancer tissues,and the three protein may play a regulatory role through the same pathway in the development and progression of invasive breast cancer.SOX7,β-catenin and cyclin D1,s abnormal expression in invasive breast cancer correlate with the clinical pathology charactersis,and the three protein may be valuable marker for assessing the prognosis for invasive breast cancer.
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Study found that in some human tumors such as breast cancer,SOX7 gene is highly likely to be a tumor suppressor gene.The tumor suppressor role of SOX7 may be accomplished by regulating the Wnt/β-catenin signaling pathway mediated the transcription process,and the abnormal Wnt/β-catenin signaling pathway is likely to play its role through the regulation of its downstream target gene Cyclin D1,etc,so that the ahnormal cell proliferation activity is unable to carry on,and thus plays the function of tumor suppressor.This review will summarize the research progress of the role of SOX7 geue and its closely related β-catenin,Cyclin D1 gene in breast cancer.