Background:A significant proportion of patients still cannot benefit from existing targeted therapies and immunotherapies,making the search for new treatment strategies extremely urgent.In this study,we combined integ...Background:A significant proportion of patients still cannot benefit from existing targeted therapies and immunotherapies,making the search for new treatment strategies extremely urgent.In this study,we combined integrate public data analysis with experimental validation to identify novel prognostic biomarkers and therapeutic targets for lung adenocarcinoma(LUAD).Methods:We analyzed RNA and protein databases to assess the expression levels of cytochrome C oxidase 5B(COX5B)in LUAD.Several computational algorithms were employed to investigate the relationship between COX5B and immune infiltration in LUAD.To further elucidate the role of COX5B in LUAD,we utilized multiple experimental approaches,including quantitative reverse transcription PCR assays,western blot,immunohistochemistry,electron microscopy,flow cytometry,and EdU proliferation assays.Results:We revealed that COX5B was significantly elevated in LUAD and positively correlated with poor prognosis of LUAD patients.Analysis of co-expression network indicated that COX5B may take part in the intracellular adenosine triphosphate(ATP)synthesis through the oxidative phosphorylation pathway.There was a negative correlation between COX5B expression and immune infiltration in LUAD.Furthermore,we validated that COX5B levels were significantly elevated in both LUAD tissues and cell lines.Specifically,immunohistochemistry(IHC)assays revealed a 2.32-fold increase of COX5B in tumor tissues compared to that in adjacent normal tissues(p=0.0044).Additionally,COX5B knockdown disrupted the redox homeostasis,ultimately suppressed the proliferation of LUAD cells.Subsequent investigations demonstrated that berberine effectively targeted COX5B,diminishing its protein expression and consequently inhibiting cell proliferation and tumor growth in LUAD.Conclusions:This study established that upregulated COX5B was positive associated with poor patient prognosis in LUAD,elucidating the mechanisms by which berberine targets COX5B to inhibit tumor growth,thereby providing a novel therapeutic target and strategy for the clinical management of LUAD.展开更多
嵌合抗原受体T细胞(chimeric antigen receptor T cells,CAR-T)的出现使得多发性骨髓瘤(multiple myeloma,MM)患者的治疗进入了一个新的阶段,但大多数患者都难逃原发耐药或疾病复发的不良结局。G蛋白偶联受体C类5组成员D(G protein-coup...嵌合抗原受体T细胞(chimeric antigen receptor T cells,CAR-T)的出现使得多发性骨髓瘤(multiple myeloma,MM)患者的治疗进入了一个新的阶段,但大多数患者都难逃原发耐药或疾病复发的不良结局。G蛋白偶联受体C类5组成员D(G protein-coupled receptor class C group 5 member D,GPRC5D)是目前MM患者的一个有前景的治疗靶点,与GPRC5D CAR-T相关的Ⅰ期临床研究也都显示出较高的反应率和疗效。文章将对现有的靶向GPRC5D CAR-T细胞最新研究进行综述,旨在通过总结讨论目前不同GPRC5D CAR-T细胞治疗复发难治性MM的研究现状,对今后的临床治疗提供更多参考。展开更多
基金supported by grants from the Guangxi Natural Science Foundation(2024GXNSFAA010150)the Guangdong Basic and Applied Basic Research Foundation(2022A1515111167).
文摘Background:A significant proportion of patients still cannot benefit from existing targeted therapies and immunotherapies,making the search for new treatment strategies extremely urgent.In this study,we combined integrate public data analysis with experimental validation to identify novel prognostic biomarkers and therapeutic targets for lung adenocarcinoma(LUAD).Methods:We analyzed RNA and protein databases to assess the expression levels of cytochrome C oxidase 5B(COX5B)in LUAD.Several computational algorithms were employed to investigate the relationship between COX5B and immune infiltration in LUAD.To further elucidate the role of COX5B in LUAD,we utilized multiple experimental approaches,including quantitative reverse transcription PCR assays,western blot,immunohistochemistry,electron microscopy,flow cytometry,and EdU proliferation assays.Results:We revealed that COX5B was significantly elevated in LUAD and positively correlated with poor prognosis of LUAD patients.Analysis of co-expression network indicated that COX5B may take part in the intracellular adenosine triphosphate(ATP)synthesis through the oxidative phosphorylation pathway.There was a negative correlation between COX5B expression and immune infiltration in LUAD.Furthermore,we validated that COX5B levels were significantly elevated in both LUAD tissues and cell lines.Specifically,immunohistochemistry(IHC)assays revealed a 2.32-fold increase of COX5B in tumor tissues compared to that in adjacent normal tissues(p=0.0044).Additionally,COX5B knockdown disrupted the redox homeostasis,ultimately suppressed the proliferation of LUAD cells.Subsequent investigations demonstrated that berberine effectively targeted COX5B,diminishing its protein expression and consequently inhibiting cell proliferation and tumor growth in LUAD.Conclusions:This study established that upregulated COX5B was positive associated with poor patient prognosis in LUAD,elucidating the mechanisms by which berberine targets COX5B to inhibit tumor growth,thereby providing a novel therapeutic target and strategy for the clinical management of LUAD.
文摘嵌合抗原受体T细胞(chimeric antigen receptor T cells,CAR-T)的出现使得多发性骨髓瘤(multiple myeloma,MM)患者的治疗进入了一个新的阶段,但大多数患者都难逃原发耐药或疾病复发的不良结局。G蛋白偶联受体C类5组成员D(G protein-coupled receptor class C group 5 member D,GPRC5D)是目前MM患者的一个有前景的治疗靶点,与GPRC5D CAR-T相关的Ⅰ期临床研究也都显示出较高的反应率和疗效。文章将对现有的靶向GPRC5D CAR-T细胞最新研究进行综述,旨在通过总结讨论目前不同GPRC5D CAR-T细胞治疗复发难治性MM的研究现状,对今后的临床治疗提供更多参考。
