Objectives:Pancreatic cancer(PC)is characterized by poor prognosis due to its limited treatment choices and delayed detection.S100A14 has been implicated in tumor progression,yet its regulatory hierarchy and functiona...Objectives:Pancreatic cancer(PC)is characterized by poor prognosis due to its limited treatment choices and delayed detection.S100A14 has been implicated in tumor progression,yet its regulatory hierarchy and functional interplay in PC remain unclear.This study aimed to define the role of S100A14 in PC progression.Methods:Integrated bioinformatic analyses of TCGA-PAAD and GSE22780 datasets identified candidate hub genes.Prognostic relevance was assessed via Kaplan-Meier and ROC analyses.Functional experiments were performed in PANC-1 and BxPC-3 cells,including qRT-PCR,CCK-8 assay,Western blotting,Transwell assay,and apoptosis assay.Co-immunoprecipitation(Co-IP)was used to verify S100A14-S100A16 interaction.CHX chase and dual-luciferase assays were employed to assess protein stability and transcriptional activity.Results:S100A14 was markedly upregulated in PC tissues and cell lines and identified as a key prognostic gene.Silencing S100A14 suppressed EMT,proliferation,invasion,and migration,while reversing S100A16-mediated p53 inhibition and enhancing apoptosis.Mechanistically,Co-IP assay confirmed the protein interaction between S100A14 and S100A16;S100A14 stabilized S100A16 protein through post-translational modification without transcriptional regulation;the S100A14/S100A16 axis reduced p53 protein stability and inhibited its transcriptional activity as well as the downstream p21 expression.Critically,knockdown of S100A14 abrogated the pro-metastatic phenotype of cancer cells.Conclusion:This study identifies S100A14 promotes PC progression by stabilizing S100A16 and suppressing the tumor-suppressive p53/p21 pathway;knockdown of S100A14 can reverse the above effects,restore p53 function,and enhance cancer cell apoptosis.Targeting the S100A14/S100A16/p53 regulatory axis could represent a promising therapeutic approach for PC.展开更多
S100钙结合蛋白家族成员S100钙结合蛋白A16(S100 calcium-binding protein A16,S100A16)在多种恶性肿瘤存在差异表达,参与肿瘤演进,在肿瘤细胞增殖、凋亡、黏附、上皮-间质转化、迁移和侵袭中发挥重要作用,可作为不良预后因素。S100A16...S100钙结合蛋白家族成员S100钙结合蛋白A16(S100 calcium-binding protein A16,S100A16)在多种恶性肿瘤存在差异表达,参与肿瘤演进,在肿瘤细胞增殖、凋亡、黏附、上皮-间质转化、迁移和侵袭中发挥重要作用,可作为不良预后因素。S100A16与肿瘤微环境中免疫细胞浸润存在关联,促使肿瘤微环境趋向免疫抑制状态,肿瘤相关内皮细胞S100A16表达水平亦与抑制性免疫微环境形成相关。此外,S100A16在肿瘤化疗抵抗中亦发挥作用。本文综述S100A16在不同肿瘤的作用机制、肿瘤免疫微环境调节、药物治疗抵抗等研究进展,旨在进一步阐明不同肿瘤的防治机制,为克服肿瘤治疗抵抗提供理论依据。展开更多
目的对云南省文山州2019年手足口病(hand,foot and mouth disease,hfmd)病原分离情况和14株柯萨奇病毒a16型(coxsackievirus a16,cv-a16)的基因特征进行分析。方法对文山州2019年hfmd实验室送到云南省疾病预防控制中心hfmd实验室的595...目的对云南省文山州2019年手足口病(hand,foot and mouth disease,hfmd)病原分离情况和14株柯萨奇病毒a16型(coxsackievirus a16,cv-a16)的基因特征进行分析。方法对文山州2019年hfmd实验室送到云南省疾病预防控制中心hfmd实验室的595份手足口病患者粪便标本进行病毒分离,并对分离到的74株肠道病毒(enterovirus,ev)vp1区基因进行扩增和测序定型,对cv-a16病毒进行基因特征和分子流行病学分析。结果共从595份标本中分离到74株ev,ev分离率为12.44%(74/595),其中a组病毒(enterovirus species a,ev-a)72株,占97.30%(72/74),ev-b组病毒2株,占2.70%(2/74),未分离到ev-c和ev-d组病毒。ev-a组病毒中,cv-a6病毒最多,共44株,占ev-a组分离数的61.11%(44/72),cv-a16次之,共14株,占ev-a组病毒的19.44%(14/72),ev-a109株,占12.50%(9/72)。基因进化分析表明,14株cv-a16均为b1基因亚型(subgenotype b1)。它们分为2个不同的进化分支(b1a和b1b),其中8株为b1a,6株为b1b。结论2019年文山州hfmd病原以cv-a6组为主,cv-a16次之。cv-a16病毒b1a和b1b两个分支同时在文山州流行。展开更多
基金supported by the Yunnan Province Liu Liang Expert Workstation(No.202305AF150148)Famous Doctor Projects of Yunnan Province(No.XDYC-MY-2022-0032)+1 种基金Yunnan Health Training Project of High Level Talents(No.L-2024029)Innovation Team Special Program of Yunnan(No.202505AS350004).
文摘Objectives:Pancreatic cancer(PC)is characterized by poor prognosis due to its limited treatment choices and delayed detection.S100A14 has been implicated in tumor progression,yet its regulatory hierarchy and functional interplay in PC remain unclear.This study aimed to define the role of S100A14 in PC progression.Methods:Integrated bioinformatic analyses of TCGA-PAAD and GSE22780 datasets identified candidate hub genes.Prognostic relevance was assessed via Kaplan-Meier and ROC analyses.Functional experiments were performed in PANC-1 and BxPC-3 cells,including qRT-PCR,CCK-8 assay,Western blotting,Transwell assay,and apoptosis assay.Co-immunoprecipitation(Co-IP)was used to verify S100A14-S100A16 interaction.CHX chase and dual-luciferase assays were employed to assess protein stability and transcriptional activity.Results:S100A14 was markedly upregulated in PC tissues and cell lines and identified as a key prognostic gene.Silencing S100A14 suppressed EMT,proliferation,invasion,and migration,while reversing S100A16-mediated p53 inhibition and enhancing apoptosis.Mechanistically,Co-IP assay confirmed the protein interaction between S100A14 and S100A16;S100A14 stabilized S100A16 protein through post-translational modification without transcriptional regulation;the S100A14/S100A16 axis reduced p53 protein stability and inhibited its transcriptional activity as well as the downstream p21 expression.Critically,knockdown of S100A14 abrogated the pro-metastatic phenotype of cancer cells.Conclusion:This study identifies S100A14 promotes PC progression by stabilizing S100A16 and suppressing the tumor-suppressive p53/p21 pathway;knockdown of S100A14 can reverse the above effects,restore p53 function,and enhance cancer cell apoptosis.Targeting the S100A14/S100A16/p53 regulatory axis could represent a promising therapeutic approach for PC.
文摘S100钙结合蛋白家族成员S100钙结合蛋白A16(S100 calcium-binding protein A16,S100A16)在多种恶性肿瘤存在差异表达,参与肿瘤演进,在肿瘤细胞增殖、凋亡、黏附、上皮-间质转化、迁移和侵袭中发挥重要作用,可作为不良预后因素。S100A16与肿瘤微环境中免疫细胞浸润存在关联,促使肿瘤微环境趋向免疫抑制状态,肿瘤相关内皮细胞S100A16表达水平亦与抑制性免疫微环境形成相关。此外,S100A16在肿瘤化疗抵抗中亦发挥作用。本文综述S100A16在不同肿瘤的作用机制、肿瘤免疫微环境调节、药物治疗抵抗等研究进展,旨在进一步阐明不同肿瘤的防治机制,为克服肿瘤治疗抵抗提供理论依据。
文摘目的对云南省文山州2019年手足口病(hand,foot and mouth disease,hfmd)病原分离情况和14株柯萨奇病毒a16型(coxsackievirus a16,cv-a16)的基因特征进行分析。方法对文山州2019年hfmd实验室送到云南省疾病预防控制中心hfmd实验室的595份手足口病患者粪便标本进行病毒分离,并对分离到的74株肠道病毒(enterovirus,ev)vp1区基因进行扩增和测序定型,对cv-a16病毒进行基因特征和分子流行病学分析。结果共从595份标本中分离到74株ev,ev分离率为12.44%(74/595),其中a组病毒(enterovirus species a,ev-a)72株,占97.30%(72/74),ev-b组病毒2株,占2.70%(2/74),未分离到ev-c和ev-d组病毒。ev-a组病毒中,cv-a6病毒最多,共44株,占ev-a组分离数的61.11%(44/72),cv-a16次之,共14株,占ev-a组病毒的19.44%(14/72),ev-a109株,占12.50%(9/72)。基因进化分析表明,14株cv-a16均为b1基因亚型(subgenotype b1)。它们分为2个不同的进化分支(b1a和b1b),其中8株为b1a,6株为b1b。结论2019年文山州hfmd病原以cv-a6组为主,cv-a16次之。cv-a16病毒b1a和b1b两个分支同时在文山州流行。
