目的探讨热休克蛋白90α(heat shock protein 90α,Hsp90α)在结肠癌中的表达及潜在的临床价值。方法采用生物信息学和免疫组化法分析结肠癌中Hsp90α的表达水平,及其与临床病理学特征、预后和免疫细胞浸润水平的关系;采用CCK-8细胞增...目的探讨热休克蛋白90α(heat shock protein 90α,Hsp90α)在结肠癌中的表达及潜在的临床价值。方法采用生物信息学和免疫组化法分析结肠癌中Hsp90α的表达水平,及其与临床病理学特征、预后和免疫细胞浸润水平的关系;采用CCK-8细胞增殖实验和平板克隆实验检测敲除Hsp90AA1前后结肠癌细胞的增殖能力。结果生物信息学分析结果显示,Hsp90AA1在结肠癌组织中异常高表达,其表达水平越高,患者预后越差;Hsp90AA1表达与CD4^(+)T细胞(Th2)、CD8^(+)T细胞、髓样抑制细胞、Tregs细胞、中性粒细胞、巨噬细胞、M1巨噬细胞、M2巨噬细胞的浸润水平呈正相关;免疫组化结果显示结肠癌组织中Hsp90α表达明显高于癌旁正常组织,Hsp90α表达与患者性别、肿瘤大小、位置、分化程度、TNM分期、淋巴结转移、脉管癌栓、神经侵犯、远处转移等无关(P>0.05),与结肠癌患者年龄具有相关性(P<0.05)。Hsp90α高表达是影响结肠癌患者预后的独立危险因素。细胞实验结果显示,敲除Hsp90AA1可抑制结肠癌细胞的生长及增殖能力。结论Hsp90α在结肠癌中高表达,可能是结肠癌预后不良的潜在分子学标志物。展开更多
Hsp90 (Heat Shock Protein 90)是一种在细胞应激条件下诱导表达的分子伴侣蛋白,在发现其可以作为癌症的诊断手段及治疗靶点后,其研究迎来了井喷式的发展。已有研究表明,Hsp90α不仅与肿瘤细胞的生存、增殖和迁移有关,还参与了肿瘤微环...Hsp90 (Heat Shock Protein 90)是一种在细胞应激条件下诱导表达的分子伴侣蛋白,在发现其可以作为癌症的诊断手段及治疗靶点后,其研究迎来了井喷式的发展。已有研究表明,Hsp90α不仅与肿瘤细胞的生存、增殖和迁移有关,还参与了肿瘤微环境的调控,其高表达与多种癌症类型的不良预后显著相关。近期的研究表明,p53也与Hsp90α拥有复杂而密切的联系,二者之间的交互作用对肿瘤的发生发展有十分重要的作用。在本综述中,我们将探讨Hsp90α在癌症发生和治疗中的作用,关注其与p53这一关键肿瘤抑制蛋白的相互作用。展开更多
Plant height(PH)is associated with lodging resistance and planting density,which is regulated by a complicated gene network.In this study,we identified a spontaneous dwarfing mutation in maize,m30,with decreased inter...Plant height(PH)is associated with lodging resistance and planting density,which is regulated by a complicated gene network.In this study,we identified a spontaneous dwarfing mutation in maize,m30,with decreased internode number and length but increased internode diameter.A candidate gene,ZmCYP90D1,which encodes a member of the cytochrome P450 family,was isolated by map-based cloning.ZmCYP90D1 was constitutively expressed and showed highest expression in basal internodes,and its protein was targeted to the nucleus.A G-to-A substitution was identified to be the causal mutation,which resulted in a truncated protein in m30.Loss of function of ZmCYP90D1 changed expression of hormoneresponsive genes,in particular brassinosteroid(BR)-responsive genes which is mainly involved in cell cycle regulation and cell wall extension and modification in plants.The concentration of typhasterol(TY),a downstream intermediate of ZmCYP90D1 in the BR pathway,was reduced.A haplotype conferring dwarfing without reducing yield was identified.ZmCYP90D1 was inferred to influence plant height and stalk diameter via hormone-mediated cell division and cell growth via the BR pathway.展开更多
BACKGROUND Pancreatic cancer(PC)is associated with some of the worst prognoses of all major cancers.Thymoquinone(TQ)has a long history in traditional medical practice and is known for its anti-cancer,anti-inflammatory...BACKGROUND Pancreatic cancer(PC)is associated with some of the worst prognoses of all major cancers.Thymoquinone(TQ)has a long history in traditional medical practice and is known for its anti-cancer,anti-inflammatory,anti-fibrosis and antioxidant pharmacological activities.Recent studies on hypoxia-inducible factor-1α(HIF-1α)and PC have shown that HIF-1αaffects the occurrence and development of PC in many aspects.In addition,TQ could inhibit the development of renal cancer by decreasing the expression of HIF-1α.Therefore,we speculate whether TQ affects HIF-1αexpression in PC cells and explore the mechanism.AIM To elucidate the effect of TQ in PC cells and the regulatory mechanism of HIF-1αexpression.METHODS Cell counting kit-8 assay,Transwell assay and flow cytometry were performed to detect the effects of TQ on the proliferative activity,migration and invasion ability and apoptosis of PANC-1 cells and normal pancreatic duct epithelial(hTERTHPNE)cells.Quantitative real-time polymerase chain reaction and western blot assay were performed to detect the expression of HIF-1αmRNA and protein in PC cells.The effects of TQ on the HIF-1αprotein initial expression pathway and ubiquitination degradation in PANC-1 cells were examined by western blot assay and co-immunoprecipitation.RESULTS TQ significantly inhibited proliferative activity,migration,and invasion ability and promoted apoptosis of PANC-1 cells;however,no significant effects on hTERT-HPNE cells were observed.TQ significantly reduced the mRNA and protein expression levels of HIF-1αin PANC-1,AsPC-1,and BxPC-3 cells.TQ significantly inhibited the expression of the HIF-1αinitial expression pathway(PI3K/AKT/mTOR)related proteins,and promoted the ubiquitination degradation of the HIF-1αprotein in PANC-1 cells.TQ had no effect on the hydroxylation and von Hippel Lindau protein mediated ubiquitination degradation of the HIF-1αprotein but affected the stability of the HIF-1αprotein by inhibiting the interaction between HIF-1αand HSP90,thus promoting its ubiquitination degradation.CONCLUSION The regulatory mechanism of TQ on HIF-1αprotein expression in PC cells was mainly to promote the ubiquitination degradation of the HIF-1αprotein by inhibiting the interaction between HIF-1αand HSP90;Secondly,TQ reduced the initial expression of HIF-1αprotein by inhibiting the PI3K/AKT/mTOR pathway.展开更多
目的研究磁共振成像(MRI)联合血清着丝粒结合蛋白U(CENPU)、热休克蛋白90α(HSP90α)在乳腺癌诊断中的临床价值。方法选取2021年1月至2023年4月在本院就诊的疑似乳腺癌患者227例进行研究,以术后病理诊断结果作为金标准,将227例疑似乳腺...目的研究磁共振成像(MRI)联合血清着丝粒结合蛋白U(CENPU)、热休克蛋白90α(HSP90α)在乳腺癌诊断中的临床价值。方法选取2021年1月至2023年4月在本院就诊的疑似乳腺癌患者227例进行研究,以术后病理诊断结果作为金标准,将227例疑似乳腺癌患者分为乳腺癌组143例,良性肿瘤组84例。对所有患者进行MRI检查,酶联免疫法检测血清HSP90α水平,qRT-PCR法检测血清CENPU水平。ROC曲线分析血清CENPU、HSP90α水平对乳腺癌的诊断价值,四表格法分析MRI检测及其联合血清CENPU、HSP90α水平对乳腺癌的诊断价值。结果乳腺癌组血清CENPU、HSP90α水平显著高于良性肿瘤组,差异具有统计学意义(P<0.05)。血清CENPU水平诊断乳腺癌的AUC为0.739,敏感性为65.73%,特异性为76.19%;HSP90α水平诊断乳腺癌的AUC为0.767,敏感性为79.72%,特异性为64.29%。MRI检查结果显示,乳腺癌患者137例,良性肿瘤患者90例;检出浸润性导管癌50例,乳腺导管内原位癌47例,乳头状瘤27例,浸润性小叶癌13例。MRI检查乳腺癌的敏感性为76.92%,特异性为67.86%,准确度为73.57%;MRI检查对乳腺癌的诊断结果与病理诊断结果具有一致性(Kappa值=0.441,P<0.05)。M R I联合血清C E N P U、HSP90α水平诊断乳腺癌的敏感性为98.60%,特异性为63.10%,准确度为85.46%;三者联合对乳腺癌的诊断结果与病理诊断结果具有较好一致性(Kappa=0.664,P<0.05);MRI联合血清CENPU、HSP90α水平诊断乳腺癌的敏感性和准确度显著高于MRI、CENPU、HSP90α单独诊断(P<0.05)。结论MRI联合血清CENPU、HSP90α对乳腺癌诊断具有重要临床价值。展开更多
文摘目的探讨热休克蛋白90α(heat shock protein 90α,Hsp90α)在结肠癌中的表达及潜在的临床价值。方法采用生物信息学和免疫组化法分析结肠癌中Hsp90α的表达水平,及其与临床病理学特征、预后和免疫细胞浸润水平的关系;采用CCK-8细胞增殖实验和平板克隆实验检测敲除Hsp90AA1前后结肠癌细胞的增殖能力。结果生物信息学分析结果显示,Hsp90AA1在结肠癌组织中异常高表达,其表达水平越高,患者预后越差;Hsp90AA1表达与CD4^(+)T细胞(Th2)、CD8^(+)T细胞、髓样抑制细胞、Tregs细胞、中性粒细胞、巨噬细胞、M1巨噬细胞、M2巨噬细胞的浸润水平呈正相关;免疫组化结果显示结肠癌组织中Hsp90α表达明显高于癌旁正常组织,Hsp90α表达与患者性别、肿瘤大小、位置、分化程度、TNM分期、淋巴结转移、脉管癌栓、神经侵犯、远处转移等无关(P>0.05),与结肠癌患者年龄具有相关性(P<0.05)。Hsp90α高表达是影响结肠癌患者预后的独立危险因素。细胞实验结果显示,敲除Hsp90AA1可抑制结肠癌细胞的生长及增殖能力。结论Hsp90α在结肠癌中高表达,可能是结肠癌预后不良的潜在分子学标志物。
文摘Hsp90 (Heat Shock Protein 90)是一种在细胞应激条件下诱导表达的分子伴侣蛋白,在发现其可以作为癌症的诊断手段及治疗靶点后,其研究迎来了井喷式的发展。已有研究表明,Hsp90α不仅与肿瘤细胞的生存、增殖和迁移有关,还参与了肿瘤微环境的调控,其高表达与多种癌症类型的不良预后显著相关。近期的研究表明,p53也与Hsp90α拥有复杂而密切的联系,二者之间的交互作用对肿瘤的发生发展有十分重要的作用。在本综述中,我们将探讨Hsp90α在癌症发生和治疗中的作用,关注其与p53这一关键肿瘤抑制蛋白的相互作用。
基金This work was supported by the National Natural Science Foundation of China(U2004144,31971893,32101743)the Key Technologies R&D Program of Henan Province(232102111080)Yunnan Academician Expert Workstation(202305AF150082).
文摘Plant height(PH)is associated with lodging resistance and planting density,which is regulated by a complicated gene network.In this study,we identified a spontaneous dwarfing mutation in maize,m30,with decreased internode number and length but increased internode diameter.A candidate gene,ZmCYP90D1,which encodes a member of the cytochrome P450 family,was isolated by map-based cloning.ZmCYP90D1 was constitutively expressed and showed highest expression in basal internodes,and its protein was targeted to the nucleus.A G-to-A substitution was identified to be the causal mutation,which resulted in a truncated protein in m30.Loss of function of ZmCYP90D1 changed expression of hormoneresponsive genes,in particular brassinosteroid(BR)-responsive genes which is mainly involved in cell cycle regulation and cell wall extension and modification in plants.The concentration of typhasterol(TY),a downstream intermediate of ZmCYP90D1 in the BR pathway,was reduced.A haplotype conferring dwarfing without reducing yield was identified.ZmCYP90D1 was inferred to influence plant height and stalk diameter via hormone-mediated cell division and cell growth via the BR pathway.
基金Supported by Health Commission of Qinghai Province,No.2021-wjzdx-18.
文摘BACKGROUND Pancreatic cancer(PC)is associated with some of the worst prognoses of all major cancers.Thymoquinone(TQ)has a long history in traditional medical practice and is known for its anti-cancer,anti-inflammatory,anti-fibrosis and antioxidant pharmacological activities.Recent studies on hypoxia-inducible factor-1α(HIF-1α)and PC have shown that HIF-1αaffects the occurrence and development of PC in many aspects.In addition,TQ could inhibit the development of renal cancer by decreasing the expression of HIF-1α.Therefore,we speculate whether TQ affects HIF-1αexpression in PC cells and explore the mechanism.AIM To elucidate the effect of TQ in PC cells and the regulatory mechanism of HIF-1αexpression.METHODS Cell counting kit-8 assay,Transwell assay and flow cytometry were performed to detect the effects of TQ on the proliferative activity,migration and invasion ability and apoptosis of PANC-1 cells and normal pancreatic duct epithelial(hTERTHPNE)cells.Quantitative real-time polymerase chain reaction and western blot assay were performed to detect the expression of HIF-1αmRNA and protein in PC cells.The effects of TQ on the HIF-1αprotein initial expression pathway and ubiquitination degradation in PANC-1 cells were examined by western blot assay and co-immunoprecipitation.RESULTS TQ significantly inhibited proliferative activity,migration,and invasion ability and promoted apoptosis of PANC-1 cells;however,no significant effects on hTERT-HPNE cells were observed.TQ significantly reduced the mRNA and protein expression levels of HIF-1αin PANC-1,AsPC-1,and BxPC-3 cells.TQ significantly inhibited the expression of the HIF-1αinitial expression pathway(PI3K/AKT/mTOR)related proteins,and promoted the ubiquitination degradation of the HIF-1αprotein in PANC-1 cells.TQ had no effect on the hydroxylation and von Hippel Lindau protein mediated ubiquitination degradation of the HIF-1αprotein but affected the stability of the HIF-1αprotein by inhibiting the interaction between HIF-1αand HSP90,thus promoting its ubiquitination degradation.CONCLUSION The regulatory mechanism of TQ on HIF-1αprotein expression in PC cells was mainly to promote the ubiquitination degradation of the HIF-1αprotein by inhibiting the interaction between HIF-1αand HSP90;Secondly,TQ reduced the initial expression of HIF-1αprotein by inhibiting the PI3K/AKT/mTOR pathway.
文摘目的研究磁共振成像(MRI)联合血清着丝粒结合蛋白U(CENPU)、热休克蛋白90α(HSP90α)在乳腺癌诊断中的临床价值。方法选取2021年1月至2023年4月在本院就诊的疑似乳腺癌患者227例进行研究,以术后病理诊断结果作为金标准,将227例疑似乳腺癌患者分为乳腺癌组143例,良性肿瘤组84例。对所有患者进行MRI检查,酶联免疫法检测血清HSP90α水平,qRT-PCR法检测血清CENPU水平。ROC曲线分析血清CENPU、HSP90α水平对乳腺癌的诊断价值,四表格法分析MRI检测及其联合血清CENPU、HSP90α水平对乳腺癌的诊断价值。结果乳腺癌组血清CENPU、HSP90α水平显著高于良性肿瘤组,差异具有统计学意义(P<0.05)。血清CENPU水平诊断乳腺癌的AUC为0.739,敏感性为65.73%,特异性为76.19%;HSP90α水平诊断乳腺癌的AUC为0.767,敏感性为79.72%,特异性为64.29%。MRI检查结果显示,乳腺癌患者137例,良性肿瘤患者90例;检出浸润性导管癌50例,乳腺导管内原位癌47例,乳头状瘤27例,浸润性小叶癌13例。MRI检查乳腺癌的敏感性为76.92%,特异性为67.86%,准确度为73.57%;MRI检查对乳腺癌的诊断结果与病理诊断结果具有一致性(Kappa值=0.441,P<0.05)。M R I联合血清C E N P U、HSP90α水平诊断乳腺癌的敏感性为98.60%,特异性为63.10%,准确度为85.46%;三者联合对乳腺癌的诊断结果与病理诊断结果具有较好一致性(Kappa=0.664,P<0.05);MRI联合血清CENPU、HSP90α水平诊断乳腺癌的敏感性和准确度显著高于MRI、CENPU、HSP90α单独诊断(P<0.05)。结论MRI联合血清CENPU、HSP90α对乳腺癌诊断具有重要临床价值。
