| First Author | Yaojia Cheng YX | Year | 2020 |
| Journal | Int J Mol Med | Volume | 45 |
| Issue | 4 | Pages | 1163-1175 |
| PubMed ID | 32124941 | Mgi Jnum | J:298478 |
| Mgi Id | MGI:6480163 | Doi | 10.3892/ijmm.2020.4487 |
| Citation | Yaojia Cheng YX, et al. (2020) Aberrant expression of the UPF1 RNA surveillance gene disturbs keratinocyte homeostasis by stabilizing AREG. Int J Mol Med 45(4):1163-1175 |
| abstractText | The upframeshift suppressor 1 homolog (UPF1) RNA surveillance gene is a core element in the nonsensemediated RNA decay (NMD) pathway, which impacts a broad spectrum of biological processes in a cellspecific manner. In the present study, the contribution of the NMD pathway to psoriasis lesions and its moderating effects on the biological processes of keratinocytes was reported. Sanger sequencing for skin scales from two patients with psoriasis identified two mRNA mutations (c.2935_2936insA and c.20302081del) in the UPF1 gene. The somatic mutants produced truncated UPF1 proteins and perturbed the NMD pathway in cells, leading to the upregulation of NMD substrates. As the most abundant epidermal growth factor receptor ligand in keratinocytes, it was concluded that amphiregulin (AREG) mRNA is a natural NMD substrate, that is dependent on its 3' untranslated region sequence. Perturbed NMD modulated keratinocyte homeostasis in an AREGdependent but nonidentical manner, which highlighted the unique characteristics of NMD in keratinocytes. By targeting AREG mRNA posttranscriptionally, the UPF1NMD pathway contributed to an imbalance between proliferation on the one hand, and apoptosis and abnormal differentiation, migration and inflammatory response on the other, in keratinocytes, which indicated a role of the NMD pathway in the full development of keratinocyterelated morbidity and skin diseases. |
