Objective To explore the expression and clinicopathological significance of RASSF1A and WT1 in recurrent epithelial ovarian cancer.Methods Sixty-three cases of patients with pathologically confirmed epithelial ovarian...Objective To explore the expression and clinicopathological significance of RASSF1A and WT1 in recurrent epithelial ovarian cancer.Methods Sixty-three cases of patients with pathologically confirmed epithelial ovarian cancer were collected in the department of Gynaecology and Obsterics of the North China University of Technology from January 2013 to December 2018.The expression of RASSF1A and WT1 were measured by IHC staining.The relation of these proteins with ovarian cancer was also analyzed.Results Compared with non-recurrent group(46.4%),the positive expression rate of RASSF1A was 17.1%in recurrent group.The positive expression rate of WT1 was 74.3%and higher than the rate of 42.8%in non-recurrent group.The reducing expression of RASSF1A was related to clinical stage,differentiation,and with ascites(P<0.05).The increasing expression of WT1 was related to pathological type,clinical stage,histological differentiation,with ascites,and lymph node metastasis(P<0.05).Conclusion Low expression of RASSF1A and high expression of WT1 may be related to recurrent epithelial ovarian cancer.展开更多
SWI 1 is a member of a new class of tumor DNA-binding proteins named as the AT-rich in- teraction domain family （ARID）, and considered to bind with AT base pairs specifically. Genomic and functional data support ARI...SWI 1 is a member of a new class of tumor DNA-binding proteins named as the AT-rich in- teraction domain family （ARID）, and considered to bind with AT base pairs specifically. Genomic and functional data support ARID1A as a tumor suppressor because AR1D1A/BAF250a （SWI1） subunit of the SWI/SNF chromatin-remodeling complex has emerged as recurrently mutated in a broad array of tumor types. But the crystal structure of SWI1 has not been solved as yet. Using docking and molecular dynamics, we predicted the DNA interaction pattern of human SWI1 ARID and made comparisons with the other two representative ARID family members, human Mrf-2 ARID and Drosophila Dri ARID. Dynamic results revealed that the N-terminal and loop L1 of SWI1 ARID bound with the DNA major groove, while the loop L2 and helix H6 bound with the minor groove. Moreover, it was found that SWI1 ARID bound with DNA apparently in a sequence-nonspecific manner. It was concluded that SWI1 ARID can form stable complex with sequence-nonspecific DNA segment comparing to Mrf-2 ARID/DNA and Dri ARID/DNA sequence-specific complexes.展开更多
AIM: To investigate the role of [breast and ovarian cancer susceptibility 1（BRCA1）-associated RING domain 1（BARD1）]/BRCA1 E3-ubiquitin ligase complex in governing the stability of mutant liver X receptor-（LXR-α...AIM: To investigate the role of [breast and ovarian cancer susceptibility 1（BRCA1）-associated RING domain 1（BARD1）]/BRCA1 E3-ubiquitin ligase complex in governing the stability of mutant liver X receptor-（LXR-α） protein in coronary heart disease（CHD） subjects.METHODS: The expression analysis of various genes was carried out by quantitative real time polymerase chain reaction and western blotting within blood mononuclear cells of human CHD subjects at various stages of coronary occlusion and their corresponding normal healthy counterparts.Immunoprecipitation experiments were performed to establish protein interactions between LXR-αand BARD1.Peripheral blood mononuclear cells were cultured and exposed to Vitamin D3 and Cisplatin to validate the degradation of mutant LXR-αprotein in CHD subjects by BARD1/BRCA1 complex.RESULTS: The expression of mutant LXR-αprotein in CHD subjects was found to decrease gradually with the severity of coronary occlusion exhibiting a strong negative correlation,r =-0.975 at P 【 0.001.Further,the expression of BARD1 and BRCA1 also increased with the disease severity,r = 0.895 and 0.873 respectively（P 【 0.001）.Immunoprecipitation studies established that BARD1/BRCA1 complex degrades mutant LXR-αvia ubiquitination.The absence of functional LXR-αprotein resulted in increased expression of inflammatory cytokines such as interleukin（IL）-6,IL-8 and interferon-and decreased expression of ABCA1（ATP-binding cassette A1）（r = 0.932,0.949,0.918 and-0.902 with respect to Gensini score;P 【 0.001）.Additionally,cell culture experiments proved that Vitamin D3 could prevent the degradation of mutant LXR-αand restore its functional activity to some extent.CONCLUSION: Mutant LXR-αprotein in CHD subjects is degraded by BARD1/BRCA1 complex and Vitamin D3 can rescue and restore its function.展开更多
文摘Objective To explore the expression and clinicopathological significance of RASSF1A and WT1 in recurrent epithelial ovarian cancer.Methods Sixty-three cases of patients with pathologically confirmed epithelial ovarian cancer were collected in the department of Gynaecology and Obsterics of the North China University of Technology from January 2013 to December 2018.The expression of RASSF1A and WT1 were measured by IHC staining.The relation of these proteins with ovarian cancer was also analyzed.Results Compared with non-recurrent group(46.4%),the positive expression rate of RASSF1A was 17.1%in recurrent group.The positive expression rate of WT1 was 74.3%and higher than the rate of 42.8%in non-recurrent group.The reducing expression of RASSF1A was related to clinical stage,differentiation,and with ascites(P<0.05).The increasing expression of WT1 was related to pathological type,clinical stage,histological differentiation,with ascites,and lymph node metastasis(P<0.05).Conclusion Low expression of RASSF1A and high expression of WT1 may be related to recurrent epithelial ovarian cancer.
基金supported by the College Scientific and Technological Innovation Project of Huazhong University of Science and Technology(No.15A263)
文摘SWI 1 is a member of a new class of tumor DNA-binding proteins named as the AT-rich in- teraction domain family （ARID）, and considered to bind with AT base pairs specifically. Genomic and functional data support ARID1A as a tumor suppressor because AR1D1A/BAF250a （SWI1） subunit of the SWI/SNF chromatin-remodeling complex has emerged as recurrently mutated in a broad array of tumor types. But the crystal structure of SWI1 has not been solved as yet. Using docking and molecular dynamics, we predicted the DNA interaction pattern of human SWI1 ARID and made comparisons with the other two representative ARID family members, human Mrf-2 ARID and Drosophila Dri ARID. Dynamic results revealed that the N-terminal and loop L1 of SWI1 ARID bound with the DNA major groove, while the loop L2 and helix H6 bound with the minor groove. Moreover, it was found that SWI1 ARID bound with DNA apparently in a sequence-nonspecific manner. It was concluded that SWI1 ARID can form stable complex with sequence-nonspecific DNA segment comparing to Mrf-2 ARID/DNA and Dri ARID/DNA sequence-specific complexes.
基金Supported by Indian Council of Medical Research,New Delhi,India
文摘AIM: To investigate the role of [breast and ovarian cancer susceptibility 1（BRCA1）-associated RING domain 1（BARD1）]/BRCA1 E3-ubiquitin ligase complex in governing the stability of mutant liver X receptor-（LXR-α） protein in coronary heart disease（CHD） subjects.METHODS: The expression analysis of various genes was carried out by quantitative real time polymerase chain reaction and western blotting within blood mononuclear cells of human CHD subjects at various stages of coronary occlusion and their corresponding normal healthy counterparts.Immunoprecipitation experiments were performed to establish protein interactions between LXR-αand BARD1.Peripheral blood mononuclear cells were cultured and exposed to Vitamin D3 and Cisplatin to validate the degradation of mutant LXR-αprotein in CHD subjects by BARD1/BRCA1 complex.RESULTS: The expression of mutant LXR-αprotein in CHD subjects was found to decrease gradually with the severity of coronary occlusion exhibiting a strong negative correlation,r =-0.975 at P 【 0.001.Further,the expression of BARD1 and BRCA1 also increased with the disease severity,r = 0.895 and 0.873 respectively（P 【 0.001）.Immunoprecipitation studies established that BARD1/BRCA1 complex degrades mutant LXR-αvia ubiquitination.The absence of functional LXR-αprotein resulted in increased expression of inflammatory cytokines such as interleukin（IL）-6,IL-8 and interferon-and decreased expression of ABCA1（ATP-binding cassette A1）（r = 0.932,0.949,0.918 and-0.902 with respect to Gensini score;P 【 0.001）.Additionally,cell culture experiments proved that Vitamin D3 could prevent the degradation of mutant LXR-αand restore its functional activity to some extent.CONCLUSION: Mutant LXR-αprotein in CHD subjects is degraded by BARD1/BRCA1 complex and Vitamin D3 can rescue and restore its function.
