机构：[1]Institute of Aging Research, School of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang 311121[2]Department of Dermatology, Affiliated Hospital, Ningbo University, Ningbo, Zhejiang 315211[3]Institute of Zoology, Chinese Academy of Sciences, Beijing 100101[4]Information Centre,First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, P.R. China昆明医科大学附属第一医院
The up-frameshift suppressor 1 homolog (UPF1) RNA surveillance gene is a core element in the nonsense-mediated RNA decay (NMD) pathway, which impacts a broad spectrum of biological processes in a cell-specific 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.2030-2081del) 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 AREG-dependent but nonidentical manner, which highlighted the unique characteristics of NMD in keratinocytes. By targeting AREG mRNA post-transcriptionally, the UPF1-NMD 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 keratinocyte-related morbidity and skin diseases.
基金：
Natural Science Foundation of Zhejiang Province, ChinaNatural Science Foundation of Zhejiang Province [LQ18H110001]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China [81802771]
第一作者机构：[1]Institute of Aging Research, School of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang 311121
共同第一作者：
通讯作者：
通讯机构：[1]Institute of Aging Research, School of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang 311121[*1]Institute of Aging Research, School of Medicine, Hangzhou Normal University, 2318 Yuhangtang Road, Hangzhou, Zhejiang 311121, P.R. China
推荐引用方式(GB/T 7714)：
YAOJIA CHENG,QIUPING LU,NANNAN SHI,et al.Aberrant expression of the UPF1 RNA surveillance gene disturbs keratinocyte homeostasis by stabilizing AREG[J].INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE.2020,45(4):1163-1175.doi:10.3892/ijmm.2020.4487.
APA：
YAOJIA CHENG,QIUPING LU,NANNAN SHI,QIONGYAN ZHOU,JINGJING RONG...&CHEN LIU.(2020).Aberrant expression of the UPF1 RNA surveillance gene disturbs keratinocyte homeostasis by stabilizing AREG.INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE,45,(4)
MLA：
YAOJIA CHENG,et al."Aberrant expression of the UPF1 RNA surveillance gene disturbs keratinocyte homeostasis by stabilizing AREG".INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE 45..4(2020):1163-1175
