ΔNp63 silencing, DNA methylation shifts, and epithelial-mesenchymal transition resulted from TAp63 genome editing in squamous cell carcinoma.

ABSTRACT: TP63 (p63) is strongly expressed in lower-grade carcinomas of the head and neck, skin, breast, and urothelium to maintain a well-differentiated phenotype. TP63 has two transcription start sites at exons 1 and 3' that produce TAp63 and ΔNp63 isoforms, respectively. The major protein, ΔNp63α, epigenetically activates genes essential for epidermal/craniofacial differentiation, including ΔNp63 itself. To examine the specific role of weakly expressed TAp63, we disrupted exon 1 using CRISPR-Cas9 homology-directed repair in a head and neck squamous cell carcinoma (SCC) line. Surprisingly, TAp63 knockout cells having either monoallelic GFP cassette insertion paired with a frameshift deletion allele or biallelic GFP cassette insertion exhibited ΔNp63 silencing. Loss of keratinocyte-specific gene ex

SUBMITTER: Katoh I 

PROVIDER: S-EPMC10544079 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature