PMID- 31804607
OWN - NLM
STAT- MEDLINE
DCOM- 20210908
LR  - 20230918
IS  - 1476-5403 (Electronic)
IS  - 1350-9047 (Print)
IS  - 1350-9047 (Linking)
VI  - 27
IP  - 6
DP  - 2020 Jun
TI  - IGF2BP2 regulates DANCR by serving as an N6-methyladenosine reader.
PG  - 1782-1794
LID - 10.1038/s41418-019-0461-z [doi]
AB  - The major function of Insulin-like growth factor 2 mRNA-binding protein 2 
      (IGF2BP2) is to regulate cell metabolism. However, emerging evidence indicates 
      that IGF2BP2 plays a role in cancer, but the underlying mechanism is largely 
      unknown. Here we showed that upregulation of IGF2BP2 is associated with poor 
      outcomes of pancreatic cancer patients and suppression of IGF2BP2 inhibits cell 
      proliferation. We further showed that IGF2BP2 regulates lncRNA DANCR. Ectopic 
      expression IGF2BP2 enhances, whereas knockdown (KD) or knockout (KO) of IGF2BP2 
      suppresses DANCR expression. Moreover, in vivo RNA precipitation and reciprocal 
      RNA immunoprecipitation revealed that IGF2BP2 interacts with DANCR. DANCR 
      promotes cell proliferation and stemness-like properties. Experiments with 
      xenograft models revealed that while ectopic expression of DANCR promotes, DANCR 
      KO suppresses tumor growth. Mechanistically, DANCR is modified at 
      N6-methyladenosine (m6A) and mutagenesis assay identified that adenosine at 664 
      of DANCR is critical to the interaction between IGF2BP2 and DANCR where IGF2BP2 
      serves a reader for m6A modified DANCR and stabilizes DANCR RNA. Together, these 
      results suggest that DANCR is a novel target for IGF2BP2 through m6A 
      modification, and IGF2BP2 and DANCR work together to promote cancer stemness-like 
      properties and pancreatic cancer pathogenesis.
FAU - Hu, Xiaoge
AU  - Hu X
AD  - Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of 
      Zhejiang Province, Zhejiang Provincial People's Hospital, People's Hospital of 
      Hangzhou Medical College, Hangzhou, 310014, Zhejiang, China.
AD  - Cancer Institute, University of Mississippi Medical Center, Jackson, MS, USA.
FAU - Peng, Wan-Xin
AU  - Peng WX
AD  - Cancer Institute, University of Mississippi Medical Center, Jackson, MS, USA.
AD  - Department of Cell biology, School of Medicine, Jiangsu University, Zhenjiang, 
      China.
FAU - Zhou, Huaixiang
AU  - Zhou H
AD  - Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of 
      Zhejiang Province, Zhejiang Provincial People's Hospital, People's Hospital of 
      Hangzhou Medical College, Hangzhou, 310014, Zhejiang, China.
FAU - Jiang, Jiahong
AU  - Jiang J
AD  - Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of 
      Zhejiang Province, Zhejiang Provincial People's Hospital, People's Hospital of 
      Hangzhou Medical College, Hangzhou, 310014, Zhejiang, China.
FAU - Zhou, Xinchun
AU  - Zhou X
AD  - Department of Pathology, University of Mississippi Medical Center, Jackson, MS, 
      USA.
FAU - Huang, Dongsheng
AU  - Huang D
AD  - Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of 
      Zhejiang Province, Zhejiang Provincial People's Hospital, People's Hospital of 
      Hangzhou Medical College, Hangzhou, 310014, Zhejiang, China.
FAU - Mo, Yin-Yuan
AU  - Mo YY
AD  - Cancer Institute, University of Mississippi Medical Center, Jackson, MS, USA. 
      ymo@umc.edu.
AD  - Department of Pharmacology/Toxicology, University of Mississippi Medical Center, 
      Jackson, MS, USA. ymo@umc.edu.
FAU - Yang, Liu
AU  - Yang L
AD  - Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of 
      Zhejiang Province, Zhejiang Provincial People's Hospital, People's Hospital of 
      Hangzhou Medical College, Hangzhou, 310014, Zhejiang, China. 
      yangliuqq2003@163.com.
LA  - eng
GR  - P20 GM121334/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20191205
PL  - England
TA  - Cell Death Differ
JT  - Cell death and differentiation
JID - 9437445
RN  - 0 (DANCR long noncoding RNA, human)
RN  - 0 (IGF2BP2 protein, human)
RN  - 0 (RNA, Long Noncoding)
RN  - 0 (RNA-Binding Proteins)
RN  - CLE6G00625 (N-methyladenosine)
RN  - K72T3FS567 (Adenosine)
SB  - IM
MH  - Adenosine/*analogs & derivatives/metabolism
MH  - Animals
MH  - Cell Line, Tumor
MH  - Cell Proliferation
MH  - Humans
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Knockout
MH  - Pancreatic Neoplasms/*metabolism
MH  - RNA, Long Noncoding/*metabolism
MH  - RNA-Binding Proteins/*physiology
PMC - PMC7244758
COIS- The authors declare that they have no conflict of interest.
EDAT- 2019/12/06 06:00
MHDA- 2021/09/09 06:00
PMCR- 2019/12/05
CRDT- 2019/12/06 06:00
PHST- 2019/05/16 00:00 [received]
PHST- 2019/11/11 00:00 [accepted]
PHST- 2019/11/02 00:00 [revised]
PHST- 2019/12/06 06:00 [pubmed]
PHST- 2021/09/09 06:00 [medline]
PHST- 2019/12/06 06:00 [entrez]
PHST- 2019/12/05 00:00 [pmc-release]
AID - 10.1038/s41418-019-0461-z [pii]
AID - 461 [pii]
AID - 10.1038/s41418-019-0461-z [doi]
PST - ppublish
SO  - Cell Death Differ. 2020 Jun;27(6):1782-1794. doi: 10.1038/s41418-019-0461-z. Epub 
      2019 Dec 5.