PMID- 34895038
OWN - NLM
STAT- MEDLINE
DCOM- 20220215
LR  - 20240226
IS  - 2165-5987 (Electronic)
IS  - 2165-5979 (Print)
IS  - 2165-5979 (Linking)
VI  - 12
IP  - 2
DP  - 2021 Dec
TI  - Ribonucleotide reductase subunit M2 promotes proliferation and 
      epithelial-mesenchymal transition via the JAK2/STAT3 signaling pathway in 
      retinoblastoma.
PG  - 12800-12811
LID - 10.1080/21655979.2021.2001241 [doi]
AB  - Retinoblastoma (RB) is an intraocular malignant tumor that often occurs in 
      children. Along with the improvement of treatment strategies, the cure rate of RB 
      has increased significantly. However, the treatment of advanced and recurrent RB 
      remains as a critical challenge. Therefore, studying the molecular mechanisms 
      underlying the progression of RB is essential for the development of novel and 
      effective therapeutic strategies. Through the analysis of a previously published 
      microarray study, we found that ribonucleotide reductase subunit M2 (RRM2) was 
      highly expressed in RB tissues as compared to normal tissues. The purpose of this 
      study is to clarify the role and mechanism of RRM2 in regulating the progression 
      of RB. We first demonstrated that RRM2 expression level in RB tissues and cell 
      lines was significantly higher when compared to that in normal retinal tissue and 
      cell lines, and high RRM2 expression level was associated with a poorer overall 
      survival of patients. In RB cells, RRM2 overexpression promoted cell 
      proliferation, migration, invasion and epithelial-mesenchymal transformation 
      (EMT), while RRM2 silencing suppressed these biological features. Silencing RRM2 
      reduced the activation of Janus kinase 2 (JAK2)/signal transducer and activator 
      of transcription 3 (STAT3) signaling pathway, and the presence of JAK2/STAT3 
      signaling pathway inhibitor INCB attenuated the effect of RRM2 overexpression. 
      Collectively, our data indicate that RRM2 promotes the progression of RB by 
      activating JAK2/STAT3 signaling pathway. Targeting RRM2/JAK2/STAT3 axis lays a 
      theoretical foundation for the formulation of novel RB therapy.
FAU - Yang, Min
AU  - Yang M
AD  - Department of Ophthalmology, Beijing Luhe Hospital, Capital Medical University, 
      Beijing, China.
FAU - Yao, Panpan
AU  - Yao P
AD  - Department of Ophthalmology Medicine, Wusong Branch, Zhongshan Hospital, Fudan 
      University, Shanghai, China.
FAU - Lang, Xuqiang
AU  - Lang X
AD  - Department of Ophthalmology, Beijing Luhe Hospital, Capital Medical University, 
      Beijing, China.
FAU - Li, Xue
AU  - Li X
AD  - Department of Ophthalmology, Beijing Luhe Hospital, Capital Medical University, 
      Beijing, China.
FAU - Zhang, Dawei
AU  - Zhang D
AD  - Department of Ophthalmology, Beijing Luhe Hospital, Capital Medical University, 
      Beijing, China.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Bioengineered
JT  - Bioengineered
JID - 101581063
RN  - 0 (Protein Subunits)
RN  - 0 (STAT3 Transcription Factor)
RN  - EC 1.17.4.- (ribonucleotide reductase M2)
RN  - EC 1.17.4.1 (Ribonucleoside Diphosphate Reductase)
RN  - EC 2.7.10.2 (Janus Kinase 2)
SB  - IM
MH  - Animals
MH  - Cell Line, Tumor
MH  - Cell Movement/genetics
MH  - Cell Proliferation/genetics
MH  - Child
MH  - Child, Preschool
MH  - *Epithelial-Mesenchymal Transition/genetics
MH  - Female
MH  - Gene Expression Regulation, Neoplastic
MH  - Gene Silencing
MH  - Humans
MH  - Janus Kinase 2/*metabolism
MH  - Male
MH  - Mice, Inbred BALB C
MH  - Mice, Nude
MH  - Neoplasm Invasiveness
MH  - Protein Subunits/*metabolism
MH  - Retinoblastoma/*metabolism
MH  - Ribonucleoside Diphosphate Reductase/genetics/*metabolism
MH  - STAT3 Transcription Factor/*metabolism
MH  - *Signal Transduction
MH  - Mice
PMC - PMC8809947
OTO - NOTNLM
OT  - EMT
OT  - JAK2/STAT3
OT  - RRM2
OT  - retinoblastoma
COIS- No potential conflict of interest was reported by the author(s).
EDAT- 2021/12/14 06:00
MHDA- 2022/02/16 06:00
PMCR- 2021/12/11
CRDT- 2021/12/13 11:30
PHST- 2021/12/13 11:30 [entrez]
PHST- 2021/12/14 06:00 [pubmed]
PHST- 2022/02/16 06:00 [medline]
PHST- 2021/12/11 00:00 [pmc-release]
AID - 2001241 [pii]
AID - 10.1080/21655979.2021.2001241 [doi]
PST - ppublish
SO  - Bioengineered. 2021 Dec;12(2):12800-12811. doi: 10.1080/21655979.2021.2001241.