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The GRHL3-regulated long non-coding RNA lnc-DC modulates keratinocytes differentiation by interacting with IGF2BP2 and up-regulating ZNF750.
- Source :
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Journal of Dermatological Science . Mar2024, Vol. 113 Issue 3, p93-102. 10p. - Publication Year :
- 2024
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Abstract
- Aberrant keratinocytes differentiation has been demonstrated to be associated with a number of skin diseases. The roles of lncRNAs in keratinocytes differentiation remain to be largely unknown. Here we aim to investigate the role of lnc-DC in regulating epidermal keratinocytes differentiation. Expression of lnc-DC in the skin was queried in AnnoLnc and verified by FISH. The lncRNA expression profiles during keratinocytes differentiation were reanalyzed and verified by qPCR and FISH. Gene knock-down and over-expression were used to explore the role of lnc-DC in keratinocytes differentiation. The downstream target of lnc-DC was screened by whole transcriptome sequencing. CUT&RUN assay and siRNAs transfection was used to reveal the regulatory effect of GRHL3 on lnc-DC. The mechanism of lnc-DC regulating ZNF750 was revealed by RIP assay and RNA stability assay. Lnc-DC was biasedly expressed in skin and up-regulated during epidermal keratinocytes differentiation. Knockdown lnc-DC repressed epidermal keratinocytes differentiation while over-express lnc-DC showed the opposite effect. GRHL3, a well-known transcription factor regulating keratinocytes differentiation, could bind to the promoter of lnc-DC and regulate its expression. By whole transcriptome sequencing, we identified that ZNF750 was a downstream target of lnc-DC during keratinocytes differentiation. Mechanistically, lnc-DC interacted with RNA binding protein IGF2BP2 to stabilize ZNF750 mRNA and up- regulated its downstream targets TINCR and KLF4. Our study revealed the novel role of GRHL3/lnc-DC/ZNF750 axis in regulating epidermal keratinocytes differentiation, which may provide new therapeutic targets of aberrant keratinocytes differentiation related skin diseases. • Long non-coding RNA lnc-DC is a positive regulator of keratinocytes differentiation. • Transcription factor GRHL3 regulates the expression of lnc-DC during keratinocytes differentiation. • ZNF750 is a target gene of lnc-DC in regulating keratinocytes differentiation. • Lnc-DC regulates the expression of ZNF750 by binding to the RBP IGF2BP2. [ABSTRACT FROM AUTHOR]
- Subjects :
- *LINCRNA
*RNA-binding proteins
KERATINOCYTE differentiation
Subjects
Details
- Language :
- English
- ISSN :
- 09231811
- Volume :
- 113
- Issue :
- 3
- Database :
- Academic Search Index
- Journal :
- Journal of Dermatological Science
- Publication Type :
- Academic Journal
- Accession number :
- 176545837
- Full Text :
- https://doi.org/10.1016/j.jdermsci.2024.02.003