The transcriptome analysis of cleft lip/palate-related PTCH1 variants in GMSM-K cells show carcinogenic potential  

作　　者：MINGZHAO LI QIAN ZHANG WENBIN HUANG SHIYING ZHANG NAN JIANG XIAOSHUAI HUANG FENG CHEN 

机构地区：[1]Department of Orthodontics,Peking University School and Hospital of Stomatology,Beijing,China [2]Central Laboratory,Peking University School and Hospital of Stomatology,Beijing,China [3]Biomedical Engineering Department,Peking University,Beijing,China

出　　处：《BIOCELL》2023年第1期205-214,共10页生物细胞（英文）

基　　金：This work was supported by the Natural Science Foundation of China(Nos.81870747,82170916);Clinical Medicine Plus X–Young Scholars Project(PKU2021LCXQ003);the Fundamental Research Funds for the Central Universities(BMU2021YJ001).

摘　　要：Cancer progression involves the sonic hedgehog(SHH)pathway,in which the receptor PTCH1 actives the downstream pathways.Dysfunction of PTCH1 can lead to nevoid basal cell carcinoma Syndrome(NBCCs)including neoplastic disease and congenital disorder.To evaluate the relationship between PTCH1 and cancer,we applied the CRISPR/Cas9 system to knock out PTCH1 in oral nontumorous epithelial cells(GMSM-K).Then we screened six PTCH1 variants associated with cleft lip/palate(CL/P),one of the congenital disorders in NBCCs,and generated PTCH1 variant and wild-type recombinant PTCH1^(−/−)GMSM-K cell lines.Transcriptome sequencing was conducted in these cell lines.The results revealed that differentially expressed genes(DEGs)in PTCH1^(−/−)GMSM-K were enriched in extracellular compartments,contributing epithelial diseases by pathway enrichment analysis.RT-PCR confirmed that KRT34,KRT81,KRT86,PDGFB,and WNT10B genes,associated with extracellular compartments were highly expressed in PTCH1^(−/−).The Kyoto Encyclopedia of Genes and Genomes analysis also suggested that DEGs are closely related to focal adhesion,transcriptional misregulation,and proteoglycans in breast and gastric cancers.Comparative analysis of samples revealed that the CL/P-associated PTCH1 variants A443G and V908G are potentially carcinogenic.These findings provide new insights into the carcinogenic potential of PTCH1 dysfunction.

关 键 词：CRISPR/Cas9 PTCH1 variant Carcinogenic potential Transcriptome sequencing 

分 类 号：R73[医药卫生—肿瘤]