Objective YAP1 plays a dual role as an oncogene and tumor suppressor gene in several tumors;differentiating between these roles may depend on the YAP1 phosphorylation pattern.The specific function of YAP1 in B cell ac...Objective YAP1 plays a dual role as an oncogene and tumor suppressor gene in several tumors;differentiating between these roles may depend on the YAP1 phosphorylation pattern.The specific function of YAP1 in B cell acute lymphoblastic leukemia(B-ALL),however,is currently unclear.Thus,in the present study,the role of YAP1 in B-ALL was investigated using relevant cell lines and patient datasets.Methods The effects of shRNA-mediated knockdown on YAP1 and LATS1 levels in the NALM6 and MOLT-4 cell lines were examined using Western blotting,quantitative real-time polymerase chain reaction,flow cytometry,immunostaining,and nude mouse subcutaneous tumorigenesis experiments.Gene expression levels of Hippo pathway-related molecules before and after verteporfin(VP)treatment were compared using RNA-Seq to identify significant Hippo pathway-related genes in NALM6 cells.Results Patients with ALL showing high YAP1 expression and low YAP1-Ser127 phosphorylation levels had worse prognoses than those with low YAP1 protein expression and high YAP1-Ser127 phosphorylation levels.YAP1-Ser127 phosphorylation levels were lower in NALM6 cells than in MOLT-4 and control cells;YAP1 was distributed in the nuclei in NALM6 cells.Knockdown of YAP1 inhibited MOLT-4 and NALM6 cell proliferation and arrested the NALM6 cell cycle in the G0/G1 phase.Before and after VP treatment,the expression of the upstream gene LATS1 was upregulated;its overexpression promoted YAP1-Ser127 phosphorylation.Further,YAP1 was distributed in the plasma.Conclusion LATS1 may downregulate YAP1-Ser127 phosphorylation and maintain B-ALL cell function;thus,VP,which targets this axis,may serve as a new therapeutic method for improving the outcomes for B-ALL patients.展开更多
核仁纺锤体相关蛋白质1(nucleolar and spindle-associated protein 1,NUSAP1)是一种微管结合蛋白,参与调节有丝分裂纺锤体微管的形成。NUSAP1在多种恶性肿瘤中高度表达,并与恶性肿瘤的发生与发展密切相关,有望作为一种新的生物标志物...核仁纺锤体相关蛋白质1(nucleolar and spindle-associated protein 1,NUSAP1)是一种微管结合蛋白,参与调节有丝分裂纺锤体微管的形成。NUSAP1在多种恶性肿瘤中高度表达,并与恶性肿瘤的发生与发展密切相关,有望作为一种新的生物标志物应用于肿瘤的临床诊断、治疗及预后评估,针对NUSAP1的靶向治疗方式可能成为治疗恶性肿瘤的新策略。本文主要对NUSAP1的生物学特征及与恶性肿瘤的发生发展关系进行综述,旨在为肿瘤诊断及治疗提供新的研究思路。展开更多
紫外线辐射已被世界卫生组织(World Health Organization,WHO)认定为一类致癌物。近年来,由于平流层臭氧的厚度下降和气溶胶、表面反射率、太阳活动和气候的变化,导致到达地球表面的紫外线辐射水平显著增加。皮肤是人体最大、最外层的器...紫外线辐射已被世界卫生组织(World Health Organization,WHO)认定为一类致癌物。近年来,由于平流层臭氧的厚度下降和气溶胶、表面反射率、太阳活动和气候的变化,导致到达地球表面的紫外线辐射水平显著增加。皮肤是人体最大、最外层的器官,也是保护机体的第一道屏障。直接暴露在紫外线辐射下会导致晒伤、炎症、光免疫抑制、光老化甚至皮肤癌。机体表面及环境中的微生物都会受到环境中紫外线辐射的影响,改变微生物组的组成和丰度。微生物组也可通过几种重要的光保护机制免受紫外线辐射的损伤。在医学领域,紫外线辐射可通过作用于某些皮肤微生物来进行疾病的治疗。多种微生物及其代谢物通过不同的分子机制也表现出了防治紫外线损伤的作用,具有良好应用前景。本文综述了紫外线辐射对皮肤微生物组产生的光生物学效应、微生物体为抵御紫外线辐射及紫外线辐射应用于临床皮肤病治疗的现状。然而,紫外线辐射对微生物组的影响仍有待进一步阐明,明确微生物对抗紫外辐射的机制,为人类预防紫外线损伤提供全新的思路。展开更多
2024年6月24日,国际著名期刊Cell Research在线发表了上海交通大学医学院附属瑞金医院沈柏用教授团队关于mRNA肿瘤疫苗研究的最新成果“Combination therapy of KRAS G12V mRNA vaccine and pembrolizumab:clinical benefit in patients...2024年6月24日,国际著名期刊Cell Research在线发表了上海交通大学医学院附属瑞金医院沈柏用教授团队关于mRNA肿瘤疫苗研究的最新成果“Combination therapy of KRAS G12V mRNA vaccine and pembrolizumab:clinical benefit in patients with advanced solid tumors”。该团队在全球范围内首次报道了针对KRAS G12V单靶点的mRNA肿瘤疫苗在实体肿瘤中的治疗效果,为传统治疗无法耐受或者耐药的晚期肿瘤患者带来了新希望。展开更多
Background:Long non-coding RNAs are important regulators in cancer biology and function either as tumor suppressors or as oncogenes.Their dysregulation has been closely associated with tumorigenesis.LINC00265 is upreg...Background:Long non-coding RNAs are important regulators in cancer biology and function either as tumor suppressors or as oncogenes.Their dysregulation has been closely associated with tumorigenesis.LINC00265 is upregulated in lung adenocarcinoma and is a prognostic biomarker of this cancer.However,the mechanism underlying its function in cancer progression remains poorly understood.Methods:Here,the regulatory role of LINC00265 in lung adenocarcinoma was examined using lung cancer cell lines,clinical samples,and xenografts.Results:We found that high levels of LINC00265 expression were associated with shorter overall survival rate of patients,whereas knockdown of LINC00265 inhibited proliferation of cancer cell lines and tumor growth in xenografts.Western blot andflow cytometry analyses indicated that silencing of LINC00265 induced autophagy and apoptosis.Moreover,we showed that LINC00265 interacted with and stabilized the transcriptional co-repressor Switch-independent 3a(SIN3A),which is a scaffold protein functioning either as a tumor repressor or as an oncogene in a context-dependent manner.Silencing of SIN3A also reduced proliferation of lung cancer cells,which was correlated with the induction of autophagy.These observations raise the possibility that LINC00265 functions to promote the oncogenic activity of SIN3A in lung adenocarcinoma.Conclusions:Ourfindings thus identify SIN3A as a LINC00265-associated protein and should help to understand the mechanism underlying LINC00265-mediated oncogenesis.展开更多
文摘Objective YAP1 plays a dual role as an oncogene and tumor suppressor gene in several tumors;differentiating between these roles may depend on the YAP1 phosphorylation pattern.The specific function of YAP1 in B cell acute lymphoblastic leukemia(B-ALL),however,is currently unclear.Thus,in the present study,the role of YAP1 in B-ALL was investigated using relevant cell lines and patient datasets.Methods The effects of shRNA-mediated knockdown on YAP1 and LATS1 levels in the NALM6 and MOLT-4 cell lines were examined using Western blotting,quantitative real-time polymerase chain reaction,flow cytometry,immunostaining,and nude mouse subcutaneous tumorigenesis experiments.Gene expression levels of Hippo pathway-related molecules before and after verteporfin(VP)treatment were compared using RNA-Seq to identify significant Hippo pathway-related genes in NALM6 cells.Results Patients with ALL showing high YAP1 expression and low YAP1-Ser127 phosphorylation levels had worse prognoses than those with low YAP1 protein expression and high YAP1-Ser127 phosphorylation levels.YAP1-Ser127 phosphorylation levels were lower in NALM6 cells than in MOLT-4 and control cells;YAP1 was distributed in the nuclei in NALM6 cells.Knockdown of YAP1 inhibited MOLT-4 and NALM6 cell proliferation and arrested the NALM6 cell cycle in the G0/G1 phase.Before and after VP treatment,the expression of the upstream gene LATS1 was upregulated;its overexpression promoted YAP1-Ser127 phosphorylation.Further,YAP1 was distributed in the plasma.Conclusion LATS1 may downregulate YAP1-Ser127 phosphorylation and maintain B-ALL cell function;thus,VP,which targets this axis,may serve as a new therapeutic method for improving the outcomes for B-ALL patients.
文摘核仁纺锤体相关蛋白质1(nucleolar and spindle-associated protein 1,NUSAP1)是一种微管结合蛋白,参与调节有丝分裂纺锤体微管的形成。NUSAP1在多种恶性肿瘤中高度表达,并与恶性肿瘤的发生与发展密切相关,有望作为一种新的生物标志物应用于肿瘤的临床诊断、治疗及预后评估,针对NUSAP1的靶向治疗方式可能成为治疗恶性肿瘤的新策略。本文主要对NUSAP1的生物学特征及与恶性肿瘤的发生发展关系进行综述,旨在为肿瘤诊断及治疗提供新的研究思路。
文摘紫外线辐射已被世界卫生组织(World Health Organization,WHO)认定为一类致癌物。近年来,由于平流层臭氧的厚度下降和气溶胶、表面反射率、太阳活动和气候的变化,导致到达地球表面的紫外线辐射水平显著增加。皮肤是人体最大、最外层的器官,也是保护机体的第一道屏障。直接暴露在紫外线辐射下会导致晒伤、炎症、光免疫抑制、光老化甚至皮肤癌。机体表面及环境中的微生物都会受到环境中紫外线辐射的影响,改变微生物组的组成和丰度。微生物组也可通过几种重要的光保护机制免受紫外线辐射的损伤。在医学领域,紫外线辐射可通过作用于某些皮肤微生物来进行疾病的治疗。多种微生物及其代谢物通过不同的分子机制也表现出了防治紫外线损伤的作用,具有良好应用前景。本文综述了紫外线辐射对皮肤微生物组产生的光生物学效应、微生物体为抵御紫外线辐射及紫外线辐射应用于临床皮肤病治疗的现状。然而,紫外线辐射对微生物组的影响仍有待进一步阐明,明确微生物对抗紫外辐射的机制,为人类预防紫外线损伤提供全新的思路。
文摘2024年6月24日,国际著名期刊Cell Research在线发表了上海交通大学医学院附属瑞金医院沈柏用教授团队关于mRNA肿瘤疫苗研究的最新成果“Combination therapy of KRAS G12V mRNA vaccine and pembrolizumab:clinical benefit in patients with advanced solid tumors”。该团队在全球范围内首次报道了针对KRAS G12V单靶点的mRNA肿瘤疫苗在实体肿瘤中的治疗效果,为传统治疗无法耐受或者耐药的晚期肿瘤患者带来了新希望。
基金supported in part by the National Natural Science Foundation of China(NSFC)(82073388 to SWM)the Natural Outstanding Youth Fund of Guangdong Province(2022B1515020090 to SWM)+1 种基金Guangdong Provincial Key Laboratory of Autophagy and Major Chronic Non-Communicable Diseases(2022B1212030003 to SWM)the Affiliated Hospital of Guangdong Medical University Clinical Research Program(LCYJ2020B005 to SWM).
文摘Background:Long non-coding RNAs are important regulators in cancer biology and function either as tumor suppressors or as oncogenes.Their dysregulation has been closely associated with tumorigenesis.LINC00265 is upregulated in lung adenocarcinoma and is a prognostic biomarker of this cancer.However,the mechanism underlying its function in cancer progression remains poorly understood.Methods:Here,the regulatory role of LINC00265 in lung adenocarcinoma was examined using lung cancer cell lines,clinical samples,and xenografts.Results:We found that high levels of LINC00265 expression were associated with shorter overall survival rate of patients,whereas knockdown of LINC00265 inhibited proliferation of cancer cell lines and tumor growth in xenografts.Western blot andflow cytometry analyses indicated that silencing of LINC00265 induced autophagy and apoptosis.Moreover,we showed that LINC00265 interacted with and stabilized the transcriptional co-repressor Switch-independent 3a(SIN3A),which is a scaffold protein functioning either as a tumor repressor or as an oncogene in a context-dependent manner.Silencing of SIN3A also reduced proliferation of lung cancer cells,which was correlated with the induction of autophagy.These observations raise the possibility that LINC00265 functions to promote the oncogenic activity of SIN3A in lung adenocarcinoma.Conclusions:Ourfindings thus identify SIN3A as a LINC00265-associated protein and should help to understand the mechanism underlying LINC00265-mediated oncogenesis.
