背景:p53基因是一种关键的肿瘤抑制基因,最初因在调控细胞周期、DNA修复及凋亡中的核心作用而被广泛研究。近年来,研究发现p53在肌肉骨骼疾病中同样发挥重要作用,p53的异常表达和功能失调被认为是这些疾病发生和发展的重要因素,但具体...背景:p53基因是一种关键的肿瘤抑制基因,最初因在调控细胞周期、DNA修复及凋亡中的核心作用而被广泛研究。近年来,研究发现p53在肌肉骨骼疾病中同样发挥重要作用,p53的异常表达和功能失调被认为是这些疾病发生和发展的重要因素,但具体作用机制及临床转化潜力尚未系统阐明。目的:综述p53在肌肉骨骼疾病中的多重作用,分析p53影响疾病进展的分子机制,并评估p53作为跨疾病治疗靶点的潜力。方法:通过检索PubMed数据库2004年1月至2024年12月的文献,以“P53,Osteoporosis,Post-Menopausal Osteoporosis,Osteoarthritis,Degenerative Arthritis,Rheumatoid Arthritis,Gout,Low Back Pains,Low Back Ache,Back Pain,Scoliosis”为检索词,纳入原始研究、综述及临床试验等文献,排除非英文文献及无关机制研究,最终筛选81篇文献进行综合分析。结果与结论:p53通过调控成骨-破骨平衡(如p53-Nedd4-Runx2轴)、软骨细胞凋亡(如miR-34a-SIRT1-p53通路)、炎症递质(如肿瘤坏死因子α/白细胞介素6)及氧化应激(如p53-SLC2A9轴)等机制,参与肌肉骨骼疾病的发生发展。p53的双向作用(促凋亡与抗炎)提示需精准调控p53活性。基于基因编辑(如CRISPR/Cas9)、小分子抑制剂(如PFT-α)及天然产物(如柚皮苷)的干预策略展现出治疗潜力,但临床转化仍需进一步验证。未来需结合多学科技术深化p53机制研究与临床实践。展开更多
This literature review explores the complex interaction between p53 and microRNAs(miRNAs)in the occurrence and progression of breast cancer(BC),the most common and lethal tumor type among women.BC is a multifactorial ...This literature review explores the complex interaction between p53 and microRNAs(miRNAs)in the occurrence and progression of breast cancer(BC),the most common and lethal tumor type among women.BC is a multifactorial disease resulting from a combination of genetic and epigenetic alterations in cell DNA,influencing proliferation,differentiation,and migration.TP53 gene,which codifies p53 protein,is a known tumor suppressor,and it plays an important role in cell maintenance as DNA repair,cell proliferation control,and apoptosis activation.TP53 expression can be modulated by several miRNAs,as miR-30c,miR-34a,and the miR-200 family,inhibiting p53 production and silencing its tumor suppressor effects.On the other hand,p53 protein can modulate several miRNAs expression,as miR-146a,miR-192,and the miR-200 family,by acting as a transcription factor or by modulating miRNA processing,interfering with BC aggressiveness and progression.Understanding the role of p53 and miRNAs in BC may aid in identifying new biomarkers and developing new targeted therapies for patient treatment.展开更多
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
文摘背景:p53基因是一种关键的肿瘤抑制基因,最初因在调控细胞周期、DNA修复及凋亡中的核心作用而被广泛研究。近年来,研究发现p53在肌肉骨骼疾病中同样发挥重要作用,p53的异常表达和功能失调被认为是这些疾病发生和发展的重要因素,但具体作用机制及临床转化潜力尚未系统阐明。目的:综述p53在肌肉骨骼疾病中的多重作用,分析p53影响疾病进展的分子机制,并评估p53作为跨疾病治疗靶点的潜力。方法:通过检索PubMed数据库2004年1月至2024年12月的文献,以“P53,Osteoporosis,Post-Menopausal Osteoporosis,Osteoarthritis,Degenerative Arthritis,Rheumatoid Arthritis,Gout,Low Back Pains,Low Back Ache,Back Pain,Scoliosis”为检索词,纳入原始研究、综述及临床试验等文献,排除非英文文献及无关机制研究,最终筛选81篇文献进行综合分析。结果与结论:p53通过调控成骨-破骨平衡(如p53-Nedd4-Runx2轴)、软骨细胞凋亡(如miR-34a-SIRT1-p53通路)、炎症递质(如肿瘤坏死因子α/白细胞介素6)及氧化应激(如p53-SLC2A9轴)等机制,参与肌肉骨骼疾病的发生发展。p53的双向作用(促凋亡与抗炎)提示需精准调控p53活性。基于基因编辑(如CRISPR/Cas9)、小分子抑制剂(如PFT-α)及天然产物(如柚皮苷)的干预策略展现出治疗潜力,但临床转化仍需进一步验证。未来需结合多学科技术深化p53机制研究与临床实践。
文摘This literature review explores the complex interaction between p53 and microRNAs(miRNAs)in the occurrence and progression of breast cancer(BC),the most common and lethal tumor type among women.BC is a multifactorial disease resulting from a combination of genetic and epigenetic alterations in cell DNA,influencing proliferation,differentiation,and migration.TP53 gene,which codifies p53 protein,is a known tumor suppressor,and it plays an important role in cell maintenance as DNA repair,cell proliferation control,and apoptosis activation.TP53 expression can be modulated by several miRNAs,as miR-30c,miR-34a,and the miR-200 family,inhibiting p53 production and silencing its tumor suppressor effects.On the other hand,p53 protein can modulate several miRNAs expression,as miR-146a,miR-192,and the miR-200 family,by acting as a transcription factor or by modulating miRNA processing,interfering with BC aggressiveness and progression.Understanding the role of p53 and miRNAs in BC may aid in identifying new biomarkers and developing new targeted therapies for patient treatment.
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.
