Screening Of Differential MRNA And LncRNA Related To Skin Basal Cell Carcinogenesis And Analysis Of The Biological Function Of CASC15

Section I: Identification of critically carcinogenesis-related genes in basal cell carcinomaBackground and objective: Basal cell carcinoma(BCC)is a frequent malignant tumor of skin cancers with high morbidity.The objective of this study was to identify critical genes and pathways related to the carcinogenesis of BCC and gain more insights into the underlying molecular mechanisms of BCC.Methods: The gene expression profiles of GSE7553 and GSE103439 were downloaded from the Gene Expression Omnibus database with 19 tumors and 6 normal skin tissues.Differentially expressed genes(DEGs)were screened between BCC samples and normal tissues,followed by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis.Subsequently,protein-protein interaction(PPI)network was constructed for these DEGs and module analysis was performed.Results: A total of 313 DEGs were obtained.Among them,222 genes were up-regulated and 91 genes were down-regulated.Enrichment analysis indicated that the up-regulated genes were significantly enriched in cell cycle and mitosis,while the down-regulated genes were mainly associated with unsaturated fatty acid metabolic process and cell differentiation.Additionally,TOP2 A,CDK1,and CCNB1 were identified as the top 3 hub genes ranked by degrees in the PPI network.Meanwhile,three sub-networks were derived,which indicated that these DEGs were significantly enriched in pathways,including ?cell cycle?,?extracellular matrix(ECM)-receptor interaction?,?basal cell carcinoma? and ?hedgehog signaling pathway?.Conclusions: The novel critical DEGs and pathways identified in this study may serve pivotal roles in the carcinogenesis of BCC and indicate more molecular targets for the treatment of BCC.Section II: Expression profile analysis identifies the long non-coding RNA landscape and the potential carcinogenic function of CASC15 in basal cell carcinomaBackground and objective: Accumulating evidence indicated that long non-coding RNAs(lnc RNAs)were involved in the initiation and progression of various human cancers.However,the roles of lnc RNAs in basal cell carcinoma(BCC)remains largely to be investigated.Therefore,the objective of this study was to comprehensively explore the lnc RNA expression profiles in BCC and the biological function of lnc RNA CASC15 in BCC cells.Materials and Methods: The gene expression profiles of GSE7553,with 15 tumors and 4 normal skin tissues,were downloaded from the Gene Expression Omnibus database.Then,the differentially expressed lnc RNAs of BCC were identified by bioinformatics analysis.The selected potential carcinogenic lnc RNA CASC15 was verified by q PCR method and inhibited via CASC15-specific si RNA transfection.Furthermore,cell proliferation was assessed using cell viability and colony formaton assays;cell apoptosis was assessed using flow cytometry;cell invasion and migration was conducted by wound healing and transwell assays.Results: A total of 43 differentially expressed lnc RNAs were identified,including 21 up-regulated lnc RNAs and 22 down-regulated lnc RNAs.The lnc RNA CASC15 expression was significantly overexpressed in BCC cells.Moreover,a series of in vitro experiments proved that knockdown of CASC15 inhibited the proliferation,migration and invasion ability of BCC cells as well as promoted the apoptosis of BCC cells.Conclusions: The present study identified the lnc RNAs landscape of BCC through data mining and bioinformatics analysis,and verified the oncogenic role of lnc RNA CASC15,which may play a pivotal role in the carcinogenesis of BCC and be a potential therapeutic target of BCC.