Long Non-coding RNA-BLACAT1 Activates The AKT1/mTOR Pathway Via CeRNA In Pathogenesis Of Psoriasis

Background:Psoriasis is a chronic relapsing inflammatory skin disease mediated by immunity.The pathogenesis of psoriasis has not been fully elucidated.Excessive keratinocyte proliferation and immune cell infiltration are its important pathological features.It is a long duration,hard-to-cure disease,serious cases,often accompanied by a series of internal medicine diseases,such as hypertension,atherosclerosis,Currently considered psoriasis as a systemic disease,seriously influencing the life quality,physical and mental health of patients.Long non-coding RNA is a kind of RNA without protein coding function,and its role in tumor pathogenesis has been widely explored.It has been found that lncRNA can participate in the regulation of keratinocyte proliferation and differentiation through various mechanisms.How is the relationship between lncRNA and progression of psoriasis is the issue we must consider.Transcription factor 1 associated with bladder cancer(BLACAT1)is a lncRNA that has received much attention in recent years.It can affect the occurrence and development of breast cancer,cervical cancer and gastric cancer,etc.However,the study of BLACAT1 in psoriasis is still blank.A deeper molecular biological correlation of lncRNA is the ceRNA mechanism which means non-coding RNA and mRNA can bind to miRNA respectively,forming endogenous competition and mutual regulation,thus mediating the regulation of related target genes(mRNA).The purpose of this study is to confirm that BLACAT1 is involved in keratinocyte proliferation through ceRNA mechanism,thus affecting the occurrence of psoriasis,to exploring a new horizon for clinical treatment of psoriasis.Methods:1.The expression of related genes in GSE13355 database was retrieved and analyzed.2.The mRNA level of BLACAT1 in psoriasis and normal skin tissues was determined by QRT-PCR.3.The expression level of BL AC AT1 was verified in animal and cell models of psoriasis.4.The impact of BLACAT1 on keratinocytes was verified by cck8 and cell apoptosis assays,and the relationship between BLACAT1 and AKT1/mTOR pathway was verified by QRT-PCR and western blot assays.5.Dual luciferase and AGO2-RIP assays verified that BLACAT and AKT1 could bind to miR-149-5p respectively;Exploring whether BLACAT1 regulates AKT1 through competitive binding to miR-149-5p,thereby promoting the growth and apoptosis of keratinocytes,and then participating in the occurrence and development of psoriasis.Results:1.The expression of BLACA1 was up-regulated in GSE13355 database,animal model and cell model of psoriasis.2.BLACAT1 can increase the proliferation capacity of keratinocytes and reduce its apoptosis;BLACAT 1 up-regulated AKT1/mTOR pathway at mRNA and protein levels.3.Dual luciferase gene reporting and RIP-AGO2 assay confirmed that both BLACAT1 and AKT1 could bind to miR149-5p.4.MiR149-5 can decrease AKTl/mTOR pathaway at mRNA and protein levels,increasing apoptosis and reducing proliferative capacity of keratinocytes,which can be reversed by BLACAT 1.Conclusion:BLACAT1 is up-regulated in psoriasis lesions,and activatting AKTl/mTOR signaling pathway through ceRN A regulation mechanism,regulatting proliferation and apoptosis of keratinocytes,and thus participate in the occurrence and development of psoriasis.