Receptor-interacting Protein Kinase 4 (RIPK4) Deficiency Modulates the Long Mon-coding RNAs (lncRNAs) Expression During Keratinocyte Differentiation
10th International Congress of the Molecular Biology Association of Türkiye, İstanbul, Türkiye, 17 - 19 Eylül 2026, ss.24, (Özet Bildiri)
- Yayın Türü: Bildiri / Özet Bildiri
- Basıldığı Şehir: İstanbul
- Basıldığı Ülke: Türkiye
- Sayfa Sayıları: ss.24
- Karadeniz Teknik Üniversitesi Adresli: Evet
Özet
Background/Aim: The epidermal barrier is established through the tightly regulated differentiation of basal keratinocytes into stratified epidermal layers. RIPK4 is an essential regulator of keratinocyte differentiation. Increasing evidence indicates that keratinocyte differentiation is also regulated by epigenetic mechanisms, with lncRNAs emerging as key regulators of this process. Although RIPK4 signaling has been extensively studied, the lncRNA landscape associated with RIPK4-mediated keratinocyte differentiation has not yet been systematically characterized. This study aimed to characterize dynamic changes in the lncRNA transcriptome induced by RIPK4 deficiency during in vitro keratinocyte differentiation. Materials and Methods: RIPK4 knockout (KO) HaCaT cells were generated using CRISPR/Cas9 system. Wild-type and RIPK4-KO cells were subjected to calcium-induced differentiation in vitro. Cells collected at differentiation days 0, 7, and 14 were analyzed by RNA sequencing. Differentially expressed lncRNAs between wild-type and RIPK4-KO cells at each differentiation stage were identified using DESeq2. Annotation and filtering were performed using Ensembl (GRCh38.p14), followed by BioMart-assisted characterization of genomic features. Results: Consistent with our previous findings, KO cells maintained a stem cell-like phenotype throughout the differentiation process, whereas control HaCaT cells underwent progressive differentiation. Differential lncRNA expression between KO and control cells increased over the course of differentiation, with 21, 39, and 70 transcripts detected on days 0, 7, and 14, respectively. Across all differentiation stages, structural and genomic characterization showed that differentially expressed lncRNAs were distributed across all chromosomes, predominantly contained two exons, and were 500–1000 bp in length. Among differentially expressed lncRNAs SALRNA1 (log2FoldChange ≥1,5; adj p≤ 5x10-2), and DANT1 (log2FoldChange≤-7; adj p≤1x10-10) were of particular interest, as they have previously been reported as a negative regulator of cellular senescence and a stem cell-state-associated lncRNA, respectively. Conclusion: Together, our findings suggest that stem cell state- and senescence-associated lncRNAs may contribute to the impaired differentiation observed in RIPK4-KO keratinocytes