Study on the Role of S100A4 in regulating CCND1 transcript to participate in abnormal proliferation of keratinocytes in psoriasis

Abstract:Objective To investigate the role of S100A4 in regulating CCND1 transcript to participate in abnormal proliferation of keratinocytes in psoriasis. Methods From May 2022 to September 2024, the experiment was conducted in the laboratory of People's Hospital of Xinjiang Uygur Autonomous Region.Immunohistochemistry was used to detect the expression of CCND1 protein in normal skin tissues and lesional tissues of patients with plaque psoriasis. siRNA was applied to silence S100A4, and transcriptome data affected by S100A4 were obtained by high-throughput sequencing(RNA-seq) followed by functional analysis. In HaCaT cells, S100A4 antibody was used for RNA immunoprecipitation with high-throughput sequencing(iRIP-seq) to prepare libraries. RNA-seq was performed to detect CCND1 expression in siCtrl and si-S100A4 groups. Results The positive rate of CCND1 protein in lesional tissues was 98%(49/50), significantly higher than 78.3%(18/23) in normal skin tissues(χ²/P=7.947/0.005). GO and KEGG analyses of RNA-seq data showed that S100A4 played important roles in regulating intercellular signaling, inflammatory response, keratinization, angiogenesis, cell adhesion, and epidermal development. Overlap analysis between differentially expressed genes after S100A4 silencing from RNA-seq and S100A4-binding peak genes identified in two iRIP-seq replicates revealed that CCND1 was included in the overlapping genes. FPKM value analysis from RNA-seq showed that the CCND1 expression was downregulated after S100A4 silencing, with a higher FPKM value in the siCtrl group than in the si-S100A4 group(P<0.001). Conclusion S100A4 binds to CCND1 and affects its expression, thereby influencing the cell cycle. Their combined action participates in the occurrence and development of psoriasis, affecting the proliferation and apoptosis of keratinocytes.