The fibrotic scar due to excessive deposition of extracellular matrix(ECM)after spinal cord injury(SCI)remains one of formidable challenges to axonal regeneration.Previous therapeutic strategies mainly focus on elimin...The fibrotic scar due to excessive deposition of extracellular matrix(ECM)after spinal cord injury(SCI)remains one of formidable challenges to axonal regeneration.Previous therapeutic strategies mainly focus on eliminating fibrotic scars by blocking(Göritz et al.,2011)or inhibiting(Dias et al.,2018)the generation of scar-forming stromal cells,as well as inducing their migratory defect(Hellal et al.,2011;Ruschel et al.,2015).展开更多
Objectives:Gastric cancer(GC)is among the most prevalent malignancies worldwide,ranking as the fifth most common cancer and the fifth leading cause of cancer-related mortality.This study intends to investigate how Inh...Objectives:Gastric cancer(GC)is among the most prevalent malignancies worldwide,ranking as the fifth most common cancer and the fifth leading cause of cancer-related mortality.This study intends to investigate how Inhibin subunit beta A(INHBA)promotes the progression of GC by activating the mitogen-activated protein kinase(MAPK)signaling pathway via targeting Integrin alpha-6(ITGA6).Methods:Quantitative reverse transcription-Polymerase Chain Reaction(qRT-PCR)and Immunohistochemistry(IHC)were utilised to validate the expression levels of INHBA in GC,which were subsequently correlated with the clinicopathological factors and outcomes.Cellular and animal studies were conducted to ascertain the role of INHBA in GC.RNA-sequencing(RNA-seq)and bioinformatics analysis were used to screen for the downstream target and pathway of INHBA,with Co-immunoprecipitation(Co-IP),Co-Immunofluorescent(Co-IF),Western blot(WB)and Rescue experiments validating their mechanisms of action in GC.Results:IHC and qRT-PCR analysis confirmed that GC tissues exhibited higher INHBA expression than adjacent noncancerous tissues.This elevated INHBA expression was found to be significantly associated with the incidence of tumor lesions,lymph node metastasis,and progression to higher TNM stages.Functional experiments showed that INHBA promoted GC cell proliferation and enhanced their migration and invasion in vitro while inhibiting apoptosis.Animal studies results indicated that INHBA overexpression promoted tumor growth and increased tumor weight and volume.Through a series of experiments,including RNA-seq,Co-IP,Co-IF,WB,and rescue assays,this study demonstrated that INHBA promotes GC progression by targeting ITGA6 to regulate the MAPK signaling pathway.Conclusions:INHBA/ITGA6/MAPK axis can provide new insights into GC therapy.Targeted INHBA inhibition holds promise as a therapeutic approach for GC treatment.展开更多
目的研究ITGA5经RNA干扰后对宫颈癌细胞生长和侵袭的影响。方法应用TNMplot、Kaplan-Meier Plotter、Human Protein Atlas数据库分析ITGA5在宫颈癌中的表达和对患者生存率的影响,采用两条靶向ITGA5的特异siRNA序列,进行RNA干扰实验。实...目的研究ITGA5经RNA干扰后对宫颈癌细胞生长和侵袭的影响。方法应用TNMplot、Kaplan-Meier Plotter、Human Protein Atlas数据库分析ITGA5在宫颈癌中的表达和对患者生存率的影响,采用两条靶向ITGA5的特异siRNA序列,进行RNA干扰实验。实验分为siITGA5#1干扰组、siITGA5#2干扰组和阴性对照组(非特异性siRNA)。实时定量PCR和Western blot法分别检测宫颈癌细胞中ITGA5的mRNA与蛋白水平,筛选内源性ITGA5呈高表达的HeLa及C-33A细胞做后续实验。Western blot法评估siRNA干扰后宫颈癌HeLa/C-33A细胞中ITGA5水平,并先后检测c-Myc、BCL-2、Bax及Vimentin、E-cadherin的表达变化,CCK-8法检测HeLa/C-33A细胞增殖,流式细胞术检测细胞凋亡,Transwell小室侵袭实验评估细胞侵袭能力。结果与阴性对照组相比,特异性siRNA显著下调宫颈癌HeLa/C-33A细胞中ITGA5蛋白的表达;宫颈癌细胞增殖明显受抑,细胞凋亡显著增加(P<0.05);c-Myc和BCL-2表达下降、Bax表达升高。干扰ITGA5后,HeLa/C-33A细胞侵袭能力显著降低,间质性标记物Vimentin的表达明显受抑,上皮细胞标记物E-cadherin表达水平明显增加。结论ITGA5经RNA干扰后,能明显抑制宫颈癌细胞生长和侵袭,ITGA5对宫颈癌细胞侵袭能力的影响可能是通过调控上皮细胞间质化来实现的。展开更多
文摘The fibrotic scar due to excessive deposition of extracellular matrix(ECM)after spinal cord injury(SCI)remains one of formidable challenges to axonal regeneration.Previous therapeutic strategies mainly focus on eliminating fibrotic scars by blocking(Göritz et al.,2011)or inhibiting(Dias et al.,2018)the generation of scar-forming stromal cells,as well as inducing their migratory defect(Hellal et al.,2011;Ruschel et al.,2015).
基金funded by Medical Science Foundation of Hebei University 2024B03Hebei Provincial Government-funded Provincial Medical Excellent Talent Project ZF2023025,ZF2024134,ZF2025045,ZF2025048,and ZF2025051+3 种基金Hebei Natural Science Foundation H2022206292,H2024206140Key R&D Program of Hebei Province 223777103D and 223777113DHebei Province County General Hospital Appropriate Health Technology Promotion Project 20220018other projects of Hebei Province SGH201501.
文摘Objectives:Gastric cancer(GC)is among the most prevalent malignancies worldwide,ranking as the fifth most common cancer and the fifth leading cause of cancer-related mortality.This study intends to investigate how Inhibin subunit beta A(INHBA)promotes the progression of GC by activating the mitogen-activated protein kinase(MAPK)signaling pathway via targeting Integrin alpha-6(ITGA6).Methods:Quantitative reverse transcription-Polymerase Chain Reaction(qRT-PCR)and Immunohistochemistry(IHC)were utilised to validate the expression levels of INHBA in GC,which were subsequently correlated with the clinicopathological factors and outcomes.Cellular and animal studies were conducted to ascertain the role of INHBA in GC.RNA-sequencing(RNA-seq)and bioinformatics analysis were used to screen for the downstream target and pathway of INHBA,with Co-immunoprecipitation(Co-IP),Co-Immunofluorescent(Co-IF),Western blot(WB)and Rescue experiments validating their mechanisms of action in GC.Results:IHC and qRT-PCR analysis confirmed that GC tissues exhibited higher INHBA expression than adjacent noncancerous tissues.This elevated INHBA expression was found to be significantly associated with the incidence of tumor lesions,lymph node metastasis,and progression to higher TNM stages.Functional experiments showed that INHBA promoted GC cell proliferation and enhanced their migration and invasion in vitro while inhibiting apoptosis.Animal studies results indicated that INHBA overexpression promoted tumor growth and increased tumor weight and volume.Through a series of experiments,including RNA-seq,Co-IP,Co-IF,WB,and rescue assays,this study demonstrated that INHBA promotes GC progression by targeting ITGA6 to regulate the MAPK signaling pathway.Conclusions:INHBA/ITGA6/MAPK axis can provide new insights into GC therapy.Targeted INHBA inhibition holds promise as a therapeutic approach for GC treatment.
