PMID- 35876041
OWN - NLM
STAT- MEDLINE
DCOM- 20220726
LR  - 20231105
IS  - 2001-1326 (Electronic)
IS  - 2001-1326 (Linking)
VI  - 12
IP  - 7
DP  - 2022 Jul
TI  - Circular RNA circ-TNPO3 inhibits clear cell renal cell carcinoma metastasis by 
      binding to IGF2BP2 and destabilizing SERPINH1 mRNA.
PG  - e994
LID - 10.1002/ctm2.994 [doi]
LID - e994
AB  - BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is a common malignant tumour 
      of the urinary tract. The major causes of poor prognosis are the lack of early 
      diagnosis and metastasis. Accumulating research reveals that circular RNAs 
      (circRNAs) can play key roles in the development and the progression of cancer. 
      However, the role of circRNAs in ccRCC is still uncertain. METHODS: The circRNAs 
      microarray (n = 4) was performed to investigate the circRNAs with differential 
      expression in ccRCC tissues. The candidate circRNA was selected based on the 
      cut-off criteria, such as circRNA expression abundance, circRNA size and the 
      design of divergent primers. The circ-transportin-3 (TNPO3) levels in ccRCC 
      tissues were tested by quantitative real-time (qRT)-PCR (n = 110). The 
      characteristics and subcellular localization of circ-TNPO3 were identified via 
      RNase R assay, qRT-PCR and fluorescence in situ hybridization (FISH). Then, we 
      explored the biological roles of circ-TNPO3 in ccRCC via the function experiments 
      in vitro and in vivo. RNA pull-down, RNA immunoprecipitation, bioinformatic 
      analysis, RNA-FISH assays and rescue assays were applied to validate the 
      interactions between circ-TNPO3, insulin-like growth factor 2 mRNA-binding 
      protein 2 (IGF2BP2) and serpin family H member 1 (SERPINH1) to uncover the 
      underlying molecular mechanisms of circ-TNPO3. RESULTS: We detected the obvious 
      downregulation of circ-TNPO3 in ccRCC compared to matched adjacent normal tissues 
      (n = 110). The lower circ-TNPO3 expression was found in ccRCC patients with 
      distant metastasis, higher World Health Organization/International Society of 
      Urologic Pathologists (WHO/ISUP) grade and more advanced tumour T stage. In vitro 
      and in vivo, circ-TNPO3 significantly suppressed the proliferation and migration 
      of ccRCC cells. Mechanistically, we elucidated that circ-TNPO3 directly bound to 
      IGF2BP2 protein and then destabilized SERPINH1 mRNA. Moreover, IGF2BP2/SERPINH1 
      axis was responsible for circ-TNPO3's function of inhibiting ccRCC metastasis. 
      Epithelial splicing regulatory protein 1 (ESRP1) was probably involved in the 
      biogenesis of circ-TNPO3. CONCLUSIONS: Circ-TNPO3 can suppress ccRCC progression 
      and metastasis via directly binding to IGF2BP2 protein and destabilizing SERPINH1 
      mRNA. Circ-TNPO3 may act as a potential target for ccRCC treatment.
CI  - (c) 2022 The Authors. Clinical and Translational Medicine published by John Wiley & 
      Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.
FAU - Pan, Xiaojuan
AU  - Pan X
AD  - College of Pharmacy, Chongqing Medical University, Chongqing, P. R. China.
FAU - Huang, Bo
AU  - Huang B
AD  - College of Pharmacy, Chongqing Medical University, Chongqing, P. R. China.
FAU - Ma, Qiang
AU  - Ma Q
AD  - College of Pharmacy, Chongqing Medical University, Chongqing, P. R. China.
FAU - Ren, Junwu
AU  - Ren J
AD  - College of Pharmacy, Chongqing Medical University, Chongqing, P. R. China.
FAU - Liu, Yuying
AU  - Liu Y
AD  - College of Pharmacy, Chongqing Medical University, Chongqing, P. R. China.
FAU - Wang, Cong
AU  - Wang C
AD  - Department of Urology, Southwest Hospital, Army Medical University, Chongqing, P. 
      R. China.
FAU - Zhang, Dawei
AU  - Zhang D
AD  - Department of Urology, Southwest Hospital, Army Medical University, Chongqing, P. 
      R. China.
FAU - Fu, Jian
AU  - Fu J
AD  - Department of Urology, Southwest Hospital, Army Medical University, Chongqing, P. 
      R. China.
FAU - Ran, Lingyu
AU  - Ran L
AD  - Department of Kidney, Southwest Hospital, Army Medical University, Chongqing, P. 
      R. China.
FAU - Yu, Ting
AU  - Yu T
AD  - Department of Clinical Laboratory, The 89th Hospital of The People's Liberation 
      Army, Weifang, P. R. China.
FAU - Li, Haiping
AU  - Li H
AD  - College of Pharmacy, Chongqing Medical University, Chongqing, P. R. China.
FAU - Wang, Xiaolin
AU  - Wang X
AD  - College of Pharmacy, Chongqing Medical University, Chongqing, P. R. China.
FAU - Yang, Feifei
AU  - Yang F
AD  - College of Pharmacy, Chongqing Medical University, Chongqing, P. R. China.
FAU - Liang, Ce
AU  - Liang C
AD  - College of Pharmacy, Chongqing Medical University, Chongqing, P. R. China.
FAU - Zhang, Yuying
AU  - Zhang Y
AD  - College of Pharmacy, Chongqing Medical University, Chongqing, P. R. China.
FAU - Wang, Shimin
AU  - Wang S
AD  - College of Pharmacy, Chongqing Medical University, Chongqing, P. R. China.
FAU - Ren, Jingjing
AU  - Ren J
AD  - Department of Clinical Laboratory, The 89th Hospital of The People's Liberation 
      Army, Weifang, P. R. China.
FAU - Li, Wei
AU  - Li W
AD  - Department of Pharmacy, Southwest Hospital, Army Medical University, Chongqing, 
      P. R. China.
FAU - Wang, Yongquan
AU  - Wang Y
AD  - Department of Urology, Southwest Hospital, Army Medical University, Chongqing, P. 
      R. China.
FAU - Xiao, Bin
AU  - Xiao B
AD  - College of Pharmacy, Chongqing Medical University, Chongqing, P. R. China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Clin Transl Med
JT  - Clinical and translational medicine
JID - 101597971
RN  - 0 (HSP47 Heat-Shock Proteins)
RN  - 0 (IGF2BP2 protein, human)
RN  - 0 (RNA, Circular)
RN  - 0 (RNA, Messenger)
RN  - 0 (RNA-Binding Proteins)
RN  - 0 (SERPINH1 protein, human)
RN  - 0 (TNPO3 protein, human)
RN  - 0 (beta Karyopherins)
RN  - 63231-63-0 (RNA)
SB  - IM
MH  - *Carcinoma, Renal Cell/genetics/metabolism/pathology
MH  - Cell Line, Tumor
MH  - Gene Expression Regulation, Neoplastic
MH  - HSP47 Heat-Shock Proteins/genetics/metabolism
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - *Kidney Neoplasms/genetics/metabolism/pathology
MH  - RNA
MH  - RNA, Circular/genetics
MH  - RNA, Messenger/genetics
MH  - RNA-Binding Proteins/genetics
MH  - beta Karyopherins/genetics/metabolism
PMC - PMC9309750
OTO - NOTNLM
OT  - IGF2BP2
OT  - SERPINH1
OT  - circ-TNPO3
OT  - clear cell renal cell carcinoma
COIS- The authors declare that there is no conflict of interest.
EDAT- 2022/07/26 06:00
MHDA- 2022/07/27 06:00
PMCR- 2022/07/25
CRDT- 2022/07/25 05:13
PHST- 2022/07/05 00:00 [revised]
PHST- 2022/01/09 00:00 [received]
PHST- 2022/07/11 00:00 [accepted]
PHST- 2022/07/25 05:13 [entrez]
PHST- 2022/07/26 06:00 [pubmed]
PHST- 2022/07/27 06:00 [medline]
PHST- 2022/07/25 00:00 [pmc-release]
AID - CTM2994 [pii]
AID - 10.1002/ctm2.994 [doi]
PST - ppublish
SO  - Clin Transl Med. 2022 Jul;12(7):e994. doi: 10.1002/ctm2.994.