The GRHL3-regulated long non-coding RNA lnc-DC modulates keratinocytes differentiation by interacting with IGF2BP2 and up-regulating ZNF750.

Hu, XT ; Wu, XF ; et al.

In: Journal of dermatological science, Jg. 113 (2024-03-01), Heft 3, S. 93-102

academicJournal

Background: 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.

Objective: Here we aim to investigate the role of lnc-DC in regulating epidermal keratinocytes differentiation.

Methods: 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.

Results: 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.

Conclusion: 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.

Titel:	The GRHL3-regulated long non-coding RNA lnc-DC modulates keratinocytes differentiation by interacting with IGF2BP2 and up-regulating ZNF750.
Autor/in / Beteiligte Person:	Hu, XT ; Wu, XF ; Sui, LM ; Ao, LQ ; Pu, CX ; Yuan, M ; Xing, W ; Xu, X
Zeitschrift:	Journal of dermatological science, Jg. 113 (2024-03-01), Heft 3, S. 93-102
Veröffentlichung:	Amsterdam : Elsevier, c1990-, 2024
Medientyp:	academicJournal
ISSN:	1873-569X (electronic)
DOI:	10.1016/j.jdermsci.2024.02.003
Schlagwort:	Humans Transcription Factors metabolism Keratinocytes metabolism Skin metabolism DNA-Binding Proteins genetics DNA-Binding Proteins metabolism RNA-Binding Proteins metabolism Tumor Suppressor Proteins metabolism RNA, Long Noncoding genetics RNA, Long Noncoding metabolism Skin Diseases metabolism
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article Language: English [J Dermatol Sci] 2024 Mar; Vol. 113 (3), pp. 93-102. <i>Date of Electronic Publication: </i>2024 Feb 12. MeSH Terms: RNA, Long Noncoding* / genetics ; RNA, Long Noncoding* / metabolism ; Skin Diseases* / metabolism ; Humans ; Transcription Factors / metabolism ; Keratinocytes / metabolism ; Skin / metabolism ; DNA-Binding Proteins / genetics ; DNA-Binding Proteins / metabolism ; RNA-Binding Proteins / metabolism ; Tumor Suppressor Proteins / metabolism Contributed Indexing: Keywords: GRHL3; IGF2BP2; Keratinocytes differentiation; Lnc-DC; ZNF750 Substance Nomenclature: 0 (RNA, Long Noncoding) ; 0 (Transcription Factors) ; 0 (GRHL3 protein, human) ; 0 (DNA-Binding Proteins) ; 0 (IGF2BP2 protein, human) ; 0 (RNA-Binding Proteins) ; 0 (ZNF750 protein, human) ; 0 (Tumor Suppressor Proteins) Entry Date(s): Date Created: 20240221 Date Completed: 20240415 Latest Revision: 20240415 Update Code: 20240415

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