Background:Oral squamous cell carcinoma(OSCC)is the most common head and neck malig-nancy with a low five-year survival rate.ATP-binding cassette subfamily B member 5(ABCB5)has been linked to tumorigenesis.However,its...Background:Oral squamous cell carcinoma(OSCC)is the most common head and neck malig-nancy with a low five-year survival rate.ATP-binding cassette subfamily B member 5(ABCB5)has been linked to tumorigenesis.However,its role in inducing OSCC remains unclear.Methods:Quantitative reverse transcription polymerase chain reaction(qRT-PCR),western blot,and immunocytochemistry(ICC)were performed to examine the level of ABCB5 in OSCC(CAL27 and HSC-3)and human oral keratinocyte(HOK).ABCB5 was knocked down in CAL27 cells using ABCB5-specific small interfering RNA(ABCB5 siRNA),and its contribution to migration,invasion,and epithelial-mesenchymal transition(EMT),a process by which epithelial cells lose their tight junction and acquire an increased migratory and invasive phenotype resembling that of mesenchymal cells,were evaluated by three-dimension and transwell migration and invasion assays,qRT-PCR and ICC.An in vivo OSCC model was established using 4-nitroquinoline-1-oxide(4NQO),a carcinogenic chemical that is commonly used to develop OSCC by destroying DNA synthesis and oxidative stress.Pathological alterations,ABCB5,and EMT markers were evaluated by H&E staining,immunohistochemistry,and qRT-PCR.Results:ABCB5 was significantly upregulated in CAL27 and HSC-3 cells as compared to HOK.Knockdown of ABCB5 significantly reduced the number of migrated and invaded CAL27 cells,accompanied by the significantly increased E-cadherin and decreased Vimentin and N-cadherin under Transforming growth factorβ(TGF-β)treatment.In vivo,as OSCC advanced,a notable rise in the expressions of ABCB5,N-cadherin,and Vimentin,while a statistical decrease in E-cadherin was demonstrated.Conclusion:ABCB5 promotes the migration,invasion,and EMT of OSCC.ABCB5 might be a new biomarker and potential therapeutic target for OSCC.展开更多
Hair loss and graying,the earliest visible signs of skin aging,are driven by the functional decline of hair follicle stem cells and their niches.To elucidate the transcriptional mechanisms involved in scalp aging,we c...Hair loss and graying,the earliest visible signs of skin aging,are driven by the functional decline of hair follicle stem cells and their niches.To elucidate the transcriptional mechanisms involved in scalp aging,we conducted a comprehensive analysis of human scalp samples using single-cell RNA sequencing and spatial transcriptomic technologies.Our study profiled the transcriptomes of 57,181 cells from scalp samples obtained from four young,six middle-aged,and one elderly individual.The integrated bioinformatic pipeline included cell clustering,spatial deconvolution,pseudotime trajectory,as well as cell-type specific gene expression,and intercellular communication analysis.An additional 92 volunteers were included,comprising 90(37 young,27 middle-aged,and 26 elderly)for trichoscopic examination,one young individual for senescence-associated β-galactosidase(SA-β-gal)staining,and one elderly individual for both MKI67 immunofluorescence and SA-β-gal staining.This approach led to several key findings:we identified three subtypes of mitotic keratinocytes that localized in the interfollicular epidermis(IFE),outer root sheath(ORS),and hair matrix,with pseudotime trajectory further confirming their transitional stage.Furthermore,in middleaged scalps,we observed activated activator protein 1(AP-1)transcription factor complex in keratinocytes,upregulated DCT gene in melanocytes,and decreased bone morphogenetic protein(BMP)and noncanonical wingless/integrated(ncWNT)signaling in dermal papilla(DP)-keratinocytes cross-talk.Due to the insufficient sample size and under-representation of elderly samples,transcriptional features associated with late aging,sex,and scalp regions were not completely captured.Nevertheless,our study provides valuable cell-resolved transcriptional insights into hair follicle aging and may support the development of future regenerative therapies.展开更多
基金the financial support from the Sichuan Science and Technology Program(No.2024JDRC0040)Luzhou Science and Technology Program(No.2023JYJ002,No.2023SYF139)+4 种基金Southwest Medical University Technology Program(No.2024ZKY018,No.2023ZD001,No.2024KQZX09)National Natural Science Foundation of China(No.82403404)NHCKey Laboratory ofNuclear TechnologyMedical Transformation(Mianyang Central Hospital)(No.2023HYX028)The Science and Technology Strategic Cooperation Programs of Deyang Stomatological Hospital and Southwest Medical University(No.2024DYKQXNYD03)the Affiliated Stomatology Hospital of Southwest Medical University Program(No.2022KQ03)。
文摘Background:Oral squamous cell carcinoma(OSCC)is the most common head and neck malig-nancy with a low five-year survival rate.ATP-binding cassette subfamily B member 5(ABCB5)has been linked to tumorigenesis.However,its role in inducing OSCC remains unclear.Methods:Quantitative reverse transcription polymerase chain reaction(qRT-PCR),western blot,and immunocytochemistry(ICC)were performed to examine the level of ABCB5 in OSCC(CAL27 and HSC-3)and human oral keratinocyte(HOK).ABCB5 was knocked down in CAL27 cells using ABCB5-specific small interfering RNA(ABCB5 siRNA),and its contribution to migration,invasion,and epithelial-mesenchymal transition(EMT),a process by which epithelial cells lose their tight junction and acquire an increased migratory and invasive phenotype resembling that of mesenchymal cells,were evaluated by three-dimension and transwell migration and invasion assays,qRT-PCR and ICC.An in vivo OSCC model was established using 4-nitroquinoline-1-oxide(4NQO),a carcinogenic chemical that is commonly used to develop OSCC by destroying DNA synthesis and oxidative stress.Pathological alterations,ABCB5,and EMT markers were evaluated by H&E staining,immunohistochemistry,and qRT-PCR.Results:ABCB5 was significantly upregulated in CAL27 and HSC-3 cells as compared to HOK.Knockdown of ABCB5 significantly reduced the number of migrated and invaded CAL27 cells,accompanied by the significantly increased E-cadherin and decreased Vimentin and N-cadherin under Transforming growth factorβ(TGF-β)treatment.In vivo,as OSCC advanced,a notable rise in the expressions of ABCB5,N-cadherin,and Vimentin,while a statistical decrease in E-cadherin was demonstrated.Conclusion:ABCB5 promotes the migration,invasion,and EMT of OSCC.ABCB5 might be a new biomarker and potential therapeutic target for OSCC.
基金supported by the Science,Technology,and Innovation Commission of Shenzhen Municipality(grant number JCYJ20220818102809021 to F.X.).
文摘Hair loss and graying,the earliest visible signs of skin aging,are driven by the functional decline of hair follicle stem cells and their niches.To elucidate the transcriptional mechanisms involved in scalp aging,we conducted a comprehensive analysis of human scalp samples using single-cell RNA sequencing and spatial transcriptomic technologies.Our study profiled the transcriptomes of 57,181 cells from scalp samples obtained from four young,six middle-aged,and one elderly individual.The integrated bioinformatic pipeline included cell clustering,spatial deconvolution,pseudotime trajectory,as well as cell-type specific gene expression,and intercellular communication analysis.An additional 92 volunteers were included,comprising 90(37 young,27 middle-aged,and 26 elderly)for trichoscopic examination,one young individual for senescence-associated β-galactosidase(SA-β-gal)staining,and one elderly individual for both MKI67 immunofluorescence and SA-β-gal staining.This approach led to several key findings:we identified three subtypes of mitotic keratinocytes that localized in the interfollicular epidermis(IFE),outer root sheath(ORS),and hair matrix,with pseudotime trajectory further confirming their transitional stage.Furthermore,in middleaged scalps,we observed activated activator protein 1(AP-1)transcription factor complex in keratinocytes,upregulated DCT gene in melanocytes,and decreased bone morphogenetic protein(BMP)and noncanonical wingless/integrated(ncWNT)signaling in dermal papilla(DP)-keratinocytes cross-talk.Due to the insufficient sample size and under-representation of elderly samples,transcriptional features associated with late aging,sex,and scalp regions were not completely captured.Nevertheless,our study provides valuable cell-resolved transcriptional insights into hair follicle aging and may support the development of future regenerative therapies.
