PMID- 32124941
OWN - NLM
STAT- MEDLINE
DCOM- 20201130
LR  - 20201130
IS  - 1791-244X (Electronic)
IS  - 1107-3756 (Print)
IS  - 1107-3756 (Linking)
VI  - 45
IP  - 4
DP  - 2020 Apr
TI  - Aberrant expression of the UPF1 RNA surveillance gene disturbs keratinocyte 
      homeostasis by stabilizing AREG.
PG  - 1163-1175
LID - 10.3892/ijmm.2020.4487 [doi]
AB  - 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.
FAU - Yaojia Cheng, Yaojia X
AU  - Yaojia Cheng YX
AD  - Institute of Aging Research, School of Medicine, Hangzhou Normal University, 
      Hangzhou, Zhejiang 311121, P.R. China.
FAU - Lu, Qiuping
AU  - Lu Q
AD  - Institute of Aging Research, School of Medicine, Hangzhou Normal University, 
      Hangzhou, Zhejiang 311121, P.R. China.
FAU - Shi, Nannan
AU  - Shi N
AD  - Institute of Aging Research, School of Medicine, Hangzhou Normal University, 
      Hangzhou, Zhejiang 311121, P.R. China.
FAU - Zhou, Qiongyan
AU  - Zhou Q
AD  - Department of Dermatology, Affiliated Hospital, Ningbo University, Ningbo, 
      Zhejiang 315211, P.R. China.
FAU - Rong, Jingjing
AU  - Rong J
AD  - Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, P.R. China.
FAU - Li, Liyun
AU  - Li L
AD  - Information Centre, First Affiliated Hospital of Kunming Medical University, 
      Kunming, Yunnan 650032, P.R. China.
FAU - Wang, Li
AU  - Wang L
AD  - Institute of Aging Research, School of Medicine, Hangzhou Normal University, 
      Hangzhou, Zhejiang 311121, P.R. China.
FAU - Liu, Chen
AU  - Liu C
AD  - Institute of Aging Research, School of Medicine, Hangzhou Normal University, 
      Hangzhou, Zhejiang 311121, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20200205
PL  - Greece
TA  - Int J Mol Med
JT  - International journal of molecular medicine
JID - 9810955
RN  - 0 (AREG protein, human)
RN  - 0 (Amphiregulin)
RN  - 0 (Areg protein, mouse)
RN  - 0 (Rent1 protein, mouse)
RN  - 0 (Trans-Activators)
RN  - EC 3.6.4.13 (RNA Helicases)
RN  - EC 3.6.4.13 (UPF1 protein, human)
SB  - IM
MH  - Amphiregulin/genetics/*metabolism
MH  - Animals
MH  - Disease Models, Animal
MH  - Female
MH  - Humans
MH  - Keratinocytes/*metabolism/pathology
MH  - Male
MH  - Mice
MH  - *Nonsense Mediated mRNA Decay
MH  - Protein Stability
MH  - Psoriasis/genetics/*metabolism/pathology
MH  - RNA Helicases/genetics/*metabolism
MH  - *Signal Transduction
MH  - Trans-Activators/*biosynthesis/genetics/*metabolism
PMC - PMC7053862
EDAT- 2020/03/04 06:00
MHDA- 2020/12/01 06:00
PMCR- 2020/02/05
CRDT- 2020/03/04 06:00
PHST- 2019/06/14 00:00 [received]
PHST- 2020/01/22 00:00 [accepted]
PHST- 2020/03/04 06:00 [pubmed]
PHST- 2020/12/01 06:00 [medline]
PHST- 2020/03/04 06:00 [entrez]
PHST- 2020/02/05 00:00 [pmc-release]
AID - ijmm-45-04-1163 [pii]
AID - 10.3892/ijmm.2020.4487 [doi]
PST - ppublish
SO  - Int J Mol Med. 2020 Apr;45(4):1163-1175. doi: 10.3892/ijmm.2020.4487. Epub 2020 
      Feb 5.