PMID- 32123579
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230926
IS  - 2058-7716 (Print)
IS  - 2058-7716 (Electronic)
IS  - 2058-7716 (Linking)
VI  - 6
DP  - 2020
TI  - NF90 stabilizes cyclin E1 mRNA through phosphorylation of NF90-Ser382 by CDK2.
PG  - 3
LID - 10.1038/s41420-020-0236-9 [doi]
LID - 3
AB  - Nuclear factor 90 (NF90), an RNA-binding protein, has been implicated in 
      regulating interleukin-2 (IL-2) and the immune response. It was recently reported 
      that NF90 is upregulated in hepatocellular carcinoma (HCC) tissues and promotes 
      HCC proliferation through upregulating cyclin E1 at the posttranscription level. 
      However, the regulation of NF90 in HCC remains unclear. We demonstrate here that 
      cyclin-dependent kinase (CDK) 2 interacts with NF90 and phosphorylated it at 
      serine382. Mechanistically, phosphorylation of NF90-Ser382 determines the nuclear 
      export of NF90 and stabilization of cyclin E1 mRNA. We also demonstrate that the 
      phosphorylation deficient mutant NF90-S382A inhibits cell growth and induces cell 
      cycle arrest at the G1 phase in HCC cells. Moreover, an NF90-S382A xenograft 
      tumor had a decreased size and weight compared with the wildtype NF90. The 
      NF90-S382A xenograft contained a significantly lower level of the proliferation 
      marker Ki-67. Additionally, in HCC patients, NF90-Ser382 phosphorylation was 
      stronger in tumor than in non-tumor tissues. Clinically, phosphorylation of 
      NF90-Ser382 is significantly associated with larger tumor sizes, higher AFP 
      levels, and shorter overall survival rates. These results suggest NF90-Ser382 
      phosphorylation serves as a potential diagnosis and prognostic marker and a 
      promising pharmacological target for HCC.
CI  - (c) The Author(s) 2020.
FAU - Ding, Donglin
AU  - Ding D
AD  - 1Key Laboratory of Metabolism and Molecular Medicine, the Ministry of Education, 
      Department of Biochemistry and Molecular Biology, School of Basic Medical 
      Sciences, Fudan University, Shanghai, China. ISNI: 0000 0001 0125 2443. GRID: 
      grid.8547.e
AD  - 2State Key Laboratory of Genetic Engineering, School of Life Science, Fudan 
      University, Shanghai, China. ISNI: 0000 0001 0125 2443. GRID: grid.8547.e
AD  - 3Department of Biochemistry and Molecular Biology, Mayo Clinic College of 
      Medicine, Rochester, MN USA. ISNI: 0000 0004 0459 167X. GRID: grid.66875.3a
FAU - Huang, Huixing
AU  - Huang H
AD  - 1Key Laboratory of Metabolism and Molecular Medicine, the Ministry of Education, 
      Department of Biochemistry and Molecular Biology, School of Basic Medical 
      Sciences, Fudan University, Shanghai, China. ISNI: 0000 0001 0125 2443. GRID: 
      grid.8547.e
AD  - 2State Key Laboratory of Genetic Engineering, School of Life Science, Fudan 
      University, Shanghai, China. ISNI: 0000 0001 0125 2443. GRID: grid.8547.e
FAU - Li, Quanfu
AU  - Li Q
AD  - 1Key Laboratory of Metabolism and Molecular Medicine, the Ministry of Education, 
      Department of Biochemistry and Molecular Biology, School of Basic Medical 
      Sciences, Fudan University, Shanghai, China. ISNI: 0000 0001 0125 2443. GRID: 
      grid.8547.e
FAU - Yu, Wenbo
AU  - Yu W
AD  - 2State Key Laboratory of Genetic Engineering, School of Life Science, Fudan 
      University, Shanghai, China. ISNI: 0000 0001 0125 2443. GRID: grid.8547.e
FAU - Wang, Chenji
AU  - Wang C
AD  - 2State Key Laboratory of Genetic Engineering, School of Life Science, Fudan 
      University, Shanghai, China. ISNI: 0000 0001 0125 2443. GRID: grid.8547.e
FAU - Ma, Haijie
AU  - Ma H
AD  - 4Laboratory of Cytobiology and Molecular Biology, The Affiliated Zhoushan 
      Hospital of Wenzhou Medical University, Zhoushan, Zhejiang China. ISNI: 0000 0001 
      0348 3990. GRID: grid.268099.c
FAU - Wu, Jiaxue
AU  - Wu J
AD  - 2State Key Laboratory of Genetic Engineering, School of Life Science, Fudan 
      University, Shanghai, China. ISNI: 0000 0001 0125 2443. GRID: grid.8547.e
FAU - Dang, Yongjun
AU  - Dang Y
AD  - 1Key Laboratory of Metabolism and Molecular Medicine, the Ministry of Education, 
      Department of Biochemistry and Molecular Biology, School of Basic Medical 
      Sciences, Fudan University, Shanghai, China. ISNI: 0000 0001 0125 2443. GRID: 
      grid.8547.e
FAU - Yu, Long
AU  - Yu L
AD  - 2State Key Laboratory of Genetic Engineering, School of Life Science, Fudan 
      University, Shanghai, China. ISNI: 0000 0001 0125 2443. GRID: grid.8547.e
FAU - Jiang, Wei
AU  - Jiang W
AUID- ORCID: 0000-0001-7615-0900
AD  - 1Key Laboratory of Metabolism and Molecular Medicine, the Ministry of Education, 
      Department of Biochemistry and Molecular Biology, School of Basic Medical 
      Sciences, Fudan University, Shanghai, China. ISNI: 0000 0001 0125 2443. GRID: 
      grid.8547.e
LA  - eng
PT  - Journal Article
DEP - 20200122
PL  - United States
TA  - Cell Death Discov
JT  - Cell death discovery
JID - 101665035
PMC - PMC7026180
OTO - NOTNLM
OT  - Diagnostic markers
OT  - Hepatocellular carcinoma
OT  - Prognostic markers
OT  - Tumour biomarkers
COIS- Conflict of interestThe authors declare that they have no conflict of interest.
EDAT- 2020/03/04 06:00
MHDA- 2020/03/04 06:01
PMCR- 2020/01/22
CRDT- 2020/03/04 06:00
PHST- 2019/11/19 00:00 [received]
PHST- 2019/12/17 00:00 [revised]
PHST- 2020/01/02 00:00 [accepted]
PHST- 2020/03/04 06:00 [entrez]
PHST- 2020/03/04 06:00 [pubmed]
PHST- 2020/03/04 06:01 [medline]
PHST- 2020/01/22 00:00 [pmc-release]
AID - 236 [pii]
AID - 10.1038/s41420-020-0236-9 [doi]
PST - epublish
SO  - Cell Death Discov. 2020 Jan 22;6:3. doi: 10.1038/s41420-020-0236-9. eCollection 
      2020.