Pancreatic cancer is one of the deadliest cancers with a very poor prognosis. Recently, there has been a significant increase in research directed towards identifying potential biomarkers that can be used to diagnose ...Pancreatic cancer is one of the deadliest cancers with a very poor prognosis. Recently, there has been a significant increase in research directed towards identifying potential biomarkers that can be used to diagnose and provide prognostic information for pancreatic cancer. These markers can be used clinically to optimize and personalize therapy for individual patients. In this review, we focused on 3 biomarkers involved in the DNA damage response pathway and the necroptosis pathway: Chromodomainhelicase-DNA binding protein 5, chromodomain-helicaseDNA binding protein 7, and mixed lineage kinase domain-like protein. The aim of this article is to review present literature provided for these biomarkers and current studies in which their effectiveness as prognostic biomarkers are analyzed in order to determine their future use as biomarkers in clinical medicine. Based on the data presented, these biomarkers warrant further investigation,and should be validated in future studies.展开更多
MRG proteins are conserved during evolution in fungi, flies, mammals and plants, and they can exhibit diversified functions. The animal MRGs were found to form various complexes to activate gene expression. Plant MRGI...MRG proteins are conserved during evolution in fungi, flies, mammals and plants, and they can exhibit diversified functions. The animal MRGs were found to form various complexes to activate gene expression. Plant MRGI/2 and MRG702 were reported to be involved in the regulation of flowering time via binding to H3K36me3- marked flowering genes. Herein, we determined the crystal structure of MRG701 chromodomain （MRG701CD）. MRG701co forms a novel dimerization fold both in crystal and in solution. Moreover, we found that the dimerization of MRG chromodomains is conserved in green plants. Our findings may provide new insights into the mechanism of MRGs in regulation of gene expression in green plants.展开更多
目的:探究染色质结构域蛋白8(chromodomain protein 8,CBX8)对人神经胶质瘤细胞增殖与凋亡的作用。方法:Western blot和RT-qPCR检测组织及细胞系中CBX8的表达。构建过表达CBX8和沉默CBX8载体,转染神经胶质瘤细胞T98G和U87MG,分别用MTT法...目的:探究染色质结构域蛋白8(chromodomain protein 8,CBX8)对人神经胶质瘤细胞增殖与凋亡的作用。方法:Western blot和RT-qPCR检测组织及细胞系中CBX8的表达。构建过表达CBX8和沉默CBX8载体,转染神经胶质瘤细胞T98G和U87MG,分别用MTT法和BrdU实验检测细胞增殖,流式细胞术检测细胞凋亡。结果:与正常脑组织和星形胶质细胞相比,神经胶质瘤组织及细胞中的CBX8蛋白和mRNA水平明显上升。在T98G和U87MG细胞中,过表达CBX8均促进细胞增殖,抑制细胞凋亡,并上调Rb/E2F1的表达水平,而沉默CBX8则作用相反。sh-E2F1转染细胞之后,cyclin D1的表达以及Bcl-2/Bax的比值降低。结论:CBX8可能通过Rb/E2F1通路调节胶质瘤细胞的增殖和凋亡。展开更多
目的:探讨染色质解旋酶DNA结合蛋白1样基因(chromodomain helicase/ATPase DNA binding protein 1-like gene,CHD1L)对前列腺癌细胞侵袭、迁移能力的影响及其可能的作用机制。方法:采用实时荧光定量PCR技术检测前列腺癌细胞株LNCAP、PC3...目的:探讨染色质解旋酶DNA结合蛋白1样基因(chromodomain helicase/ATPase DNA binding protein 1-like gene,CHD1L)对前列腺癌细胞侵袭、迁移能力的影响及其可能的作用机制。方法:采用实时荧光定量PCR技术检测前列腺癌细胞株LNCAP、PC3、DU145以及前列腺上皮细胞株RWPE-1中CHD1L mRNA表达水平;转染siRNA干扰前列腺癌PC3细胞CHD1L的表达,并用Transwell侵袭实验和划痕实验分析沉默CHD1L对前列腺癌细胞侵袭和迁移能力的影响;Western blotting检测PC3细胞MMP-9、N-钙黏蛋白和E-钙黏蛋白的表达水平。结果:CHD1L mRNA在前列腺癌细胞中的表达水平明显高于前列腺上皮细胞(P<0.01),其中以前列腺癌PC3细胞的表达水平最高。侵袭实验中,干扰组的穿膜细胞数明显低于阴性对照组和空白对照组[(49.67±6.67)vs(113.67±5.69)和(112.00±12.49)个,P<0.05)。划痕实验中,干扰组48 h伤口愈合率也低于阴性对照组和空白对照组[(21.27±3.27)%vs(48.47±5.72)%和(49.93±3.35)%,P<0.05]。干扰组细胞MMP-9和N-钙黏蛋白表达下调,E-钙黏蛋白表达上调。结论:沉默CHD1L可降低前列腺癌PC3细胞的侵袭迁移能力,该作用可能是通过调控MMP-9和EMT相关蛋白表达实现的。展开更多
This investigation aimed to unveil new prospective diagnosis-related biomarkers together with treatment targets against glioblastoma.Methods:The expression levels of long non-coding RNA(lncRNA)DPP10-AS1 were assessed ...This investigation aimed to unveil new prospective diagnosis-related biomarkers together with treatment targets against glioblastoma.Methods:The expression levels of long non-coding RNA(lncRNA)DPP10-AS1 were assessed using real-time quantitative polymerase chain reaction(RT-qPCR)within both the patient tissue specimens and glioblastoma cell lines.The relationship between lncRNA DPP10-AS1 expression in glioblastoma and patient prognosis was investigated.Cell Counting Kit-8(CCK-8),transwell,and clonogenic experiments were utilized to assess tumor cells’proliferation,invasiveness,and migratory potentials after lncRNA DPP10-AS1 expression was up or down-regulated.Using an online bioinformatics prediction tool,the intracellular localization of lncRNA DPP10-AS1 and its target miRNA were predicted,and RNA-FISH verified results.A dual-luciferase reporter experiment validated the relationship across miR-24-3p together with lncRNA DPP10-AS1.MiR-24-3p expression within glioblastoma was identified through RT-qPCR,and potential link across miR-24-3p and lncRNA DPP10-AS1 was assessed using Pearson correlation analysis.Moreover,influence from lncRNA DPP10-AS1/miR-24-3p axis upon glioblastoma cell progression was assessed in vivo via a subcutaneous xenograft tumor model.Results:The expression of lncRNA DPP10-AS1 was notably reduced in both surgical specimens of glioblastoma and the equivalent cell lines.Low level of lncRNA DPP10-AS1 in glioblastoma is following poor prognosis.The downregulation of lncRNA DPP10-AS1 in glioblastoma cells resulted in enhanced cellular proliferation,migration,and invasion capabilities,accompanied by downregulated E-cadherin and upregulated vimentin and N-cadherin.Additionally,the observed upregulation of lncRNA DPP10-AS1 demonstrated a substantial inhibitory function upon proliferation,invasion,and migratory capabilities of LN229 cells.Subcellular localization disclosed that lncRNA DPP10-AS1 had a binding site that interacted with miR-24-3p.Upregulated miR-24-3p was detected in glioblastomas,displaying an inverse correlation with lncRNA DPP10-AS1 expression.MiR-24-3p downstream target has been determined as chromodomain helicase DNA binding protein 5(CHD5).LncRNA DPP10-AS1 affected the invasion and proliferation of glioblastoma by controlling the miR-24-3p/CHD5 axis.Conclusion:The present study demonstrated that lncRNA DPP10-AS1 can inhibit the invasive,migratory,and proliferative properties of glioblastoma by regulating the miR-24-3p/CHD5 signaling pathway.Consequently,lncRNA DPP10-AS1 has potential as a tumor suppressor and might be utilized for accurate diagnosis and targeted treatments of glioblastomas.展开更多
基金Supported by The National Center for Advancing Translational Sciences of the National Institutes of Health under award numbers ULl TR000454 previously awarded to Dr.Colbert and Dr.Fisher and TLlT R000456 to Dr.ColbertPancreatic Cancer Action Network(Pan-CAN)&sol American Association for Cancer Research(AACR)award 16982+1 种基金Department of Defense(DOD)/Peer Reviewed Cancer Research Program(PRCRP)award CA110535Georgia Cancer Coalition award 11072,all to Dr.Yu
文摘Pancreatic cancer is one of the deadliest cancers with a very poor prognosis. Recently, there has been a significant increase in research directed towards identifying potential biomarkers that can be used to diagnose and provide prognostic information for pancreatic cancer. These markers can be used clinically to optimize and personalize therapy for individual patients. In this review, we focused on 3 biomarkers involved in the DNA damage response pathway and the necroptosis pathway: Chromodomainhelicase-DNA binding protein 5, chromodomain-helicaseDNA binding protein 7, and mixed lineage kinase domain-like protein. The aim of this article is to review present literature provided for these biomarkers and current studies in which their effectiveness as prognostic biomarkers are analyzed in order to determine their future use as biomarkers in clinical medicine. Based on the data presented, these biomarkers warrant further investigation,and should be validated in future studies.
文摘MRG proteins are conserved during evolution in fungi, flies, mammals and plants, and they can exhibit diversified functions. The animal MRGs were found to form various complexes to activate gene expression. Plant MRGI/2 and MRG702 were reported to be involved in the regulation of flowering time via binding to H3K36me3- marked flowering genes. Herein, we determined the crystal structure of MRG701 chromodomain （MRG701CD）. MRG701co forms a novel dimerization fold both in crystal and in solution. Moreover, we found that the dimerization of MRG chromodomains is conserved in green plants. Our findings may provide new insights into the mechanism of MRGs in regulation of gene expression in green plants.
文摘目的:探究染色质结构域蛋白8(chromodomain protein 8,CBX8)对人神经胶质瘤细胞增殖与凋亡的作用。方法:Western blot和RT-qPCR检测组织及细胞系中CBX8的表达。构建过表达CBX8和沉默CBX8载体,转染神经胶质瘤细胞T98G和U87MG,分别用MTT法和BrdU实验检测细胞增殖,流式细胞术检测细胞凋亡。结果:与正常脑组织和星形胶质细胞相比,神经胶质瘤组织及细胞中的CBX8蛋白和mRNA水平明显上升。在T98G和U87MG细胞中,过表达CBX8均促进细胞增殖,抑制细胞凋亡,并上调Rb/E2F1的表达水平,而沉默CBX8则作用相反。sh-E2F1转染细胞之后,cyclin D1的表达以及Bcl-2/Bax的比值降低。结论:CBX8可能通过Rb/E2F1通路调节胶质瘤细胞的增殖和凋亡。
基金supported through the Natural Science Foundation of Jiangsu Province(No.BK20201172)the Key Project of the Jiangsu Health Commission(No.ZDB2020016)the Jiangsu Province Key Research and Development Program:Social Development Project(No.BE2021653).
文摘This investigation aimed to unveil new prospective diagnosis-related biomarkers together with treatment targets against glioblastoma.Methods:The expression levels of long non-coding RNA(lncRNA)DPP10-AS1 were assessed using real-time quantitative polymerase chain reaction(RT-qPCR)within both the patient tissue specimens and glioblastoma cell lines.The relationship between lncRNA DPP10-AS1 expression in glioblastoma and patient prognosis was investigated.Cell Counting Kit-8(CCK-8),transwell,and clonogenic experiments were utilized to assess tumor cells’proliferation,invasiveness,and migratory potentials after lncRNA DPP10-AS1 expression was up or down-regulated.Using an online bioinformatics prediction tool,the intracellular localization of lncRNA DPP10-AS1 and its target miRNA were predicted,and RNA-FISH verified results.A dual-luciferase reporter experiment validated the relationship across miR-24-3p together with lncRNA DPP10-AS1.MiR-24-3p expression within glioblastoma was identified through RT-qPCR,and potential link across miR-24-3p and lncRNA DPP10-AS1 was assessed using Pearson correlation analysis.Moreover,influence from lncRNA DPP10-AS1/miR-24-3p axis upon glioblastoma cell progression was assessed in vivo via a subcutaneous xenograft tumor model.Results:The expression of lncRNA DPP10-AS1 was notably reduced in both surgical specimens of glioblastoma and the equivalent cell lines.Low level of lncRNA DPP10-AS1 in glioblastoma is following poor prognosis.The downregulation of lncRNA DPP10-AS1 in glioblastoma cells resulted in enhanced cellular proliferation,migration,and invasion capabilities,accompanied by downregulated E-cadherin and upregulated vimentin and N-cadherin.Additionally,the observed upregulation of lncRNA DPP10-AS1 demonstrated a substantial inhibitory function upon proliferation,invasion,and migratory capabilities of LN229 cells.Subcellular localization disclosed that lncRNA DPP10-AS1 had a binding site that interacted with miR-24-3p.Upregulated miR-24-3p was detected in glioblastomas,displaying an inverse correlation with lncRNA DPP10-AS1 expression.MiR-24-3p downstream target has been determined as chromodomain helicase DNA binding protein 5(CHD5).LncRNA DPP10-AS1 affected the invasion and proliferation of glioblastoma by controlling the miR-24-3p/CHD5 axis.Conclusion:The present study demonstrated that lncRNA DPP10-AS1 can inhibit the invasive,migratory,and proliferative properties of glioblastoma by regulating the miR-24-3p/CHD5 signaling pathway.Consequently,lncRNA DPP10-AS1 has potential as a tumor suppressor and might be utilized for accurate diagnosis and targeted treatments of glioblastomas.
