PMID- 35646637
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220716
IS  - 2234-943X (Print)
IS  - 2234-943X (Electronic)
IS  - 2234-943X (Linking)
VI  - 12
DP  - 2022
TI  - Exosomal Circsafb2 Reshaping Tumor Environment to Promote Renal Cell Carcinoma 
      Progression by Mediating M2 Macrophage Polarization.
PG  - 808888
LID - 10.3389/fonc.2022.808888 [doi]
LID - 808888
AB  - BACKGROUND: Macrophages are the most abundant infiltrating immune-related stromal 
      cells present in and around tumors, showing different phenotypes and functions. 
      M2 macrophages mainly exert immunosuppressive functions and promote tumor growth. 
      Exosomes are emerging as important mediators of cross-talk between tumor cells 
      and the microenvironment. CircRNAs are novel members of non-coding RNAs that 
      regulate cancer proliferation and progression. However, the mechanism by which 
      exosomal circRNA regulates macrophage polarization in renal cell carcinoma (RCC) 
      is still largely unknown. METHODS: RCC-derived exosomes were characterized using 
      transmission electron microscopy and nanoparticle tracking analysis (NTA). CCK-8, 
      wound healing, and Transwell assays were performed to assess whether exosomes 
      would affect the proliferation, migration, and invasion of RCC. Furthermore, we 
      performed a bioinformatics analysis to identify circRNAs in RCC serum-derived 
      exosomes from the GEO database. The fluorescence in situ hybridization (FISH) 
      assay was used to detect the cellular distribution of circSAFB2. Bioinformatics 
      analyses (StarBase 2.0) were used to pool the miRNA targets of circSAFB2. 
      Luciferase assays were performed to verify the direct interactions. Western 
      blotting was used to detect markers of macrophage M2 polarization. Lastly, mouse 
      xenograft and bioluminescence imaging were used to examine the clinical relevance 
      of exosomal circSAFB2 in vivo. RESULTS: We report the circRNA derived from SAFB2 
      and evaluate its biological function in promoting the immune escape of RCC. We 
      found that circSAFB2 was highly expressed in RCC tissues and RCC-derived 
      exosomes. Furthermore, we demonstrated that exosomal circSAFB2 mediates the 
      polarization of M2 macrophages through the miR-620/JAK1/STAT3 axis to promote RCC 
      metastasis. CONCLUSIONS: Our data first demonstrated that circSAFB2 leads to 
      immune escape from RCC by mediating M2 macrophage polarization via the 
      miR-620/JAK1/STAT3 axis. These findings indicate a novel molecular mechanism of 
      exosomal circSAFB2 in the progression of RCC and implicate circSAFB2 as a target 
      for exosome-mediated tumor immune evasion.
CI  - Copyright (c) 2022 Huang, Wang, Guan, Zheng, Hao, Sheng, Wang, Xu, Guo and Yao.
FAU - Huang, Xin
AU  - Huang X
AD  - Department of Nephrology, The First Hospital of China Medical University, 
      Shenyang, China.
FAU - Wang, Jingyu
AU  - Wang J
AD  - Department of Nephrology, The First Hospital of China Medical University, 
      Shenyang, China.
FAU - Guan, Jibin
AU  - Guan J
AD  - Masonic cancer center, University of Minnesota, Minneapolis, MN, United States.
FAU - Zheng, Zhong
AU  - Zheng Z
AD  - Department of Chemistry Justus Liebig University Giessen, Giessen, Germany.
FAU - Hao, JunFeng
AU  - Hao J
AD  - Institute of Nephrology, Affiliated Hospital of Guangdong Medical University, 
      Zhanjiang, China.
FAU - Sheng, Zitong
AU  - Sheng Z
AD  - Department of Nephrology, The First Hospital of China Medical University, 
      Shenyang, China.
FAU - Wang, Menghua
AU  - Wang M
AD  - Department of Nephrology, The First Hospital of China Medical University, 
      Shenyang, China.
FAU - Xu, Tianhua
AU  - Xu T
AD  - Department of Nephrology, The First Hospital of China Medical University, 
      Shenyang, China.
FAU - Guo, Guangying
AU  - Guo G
AD  - Department of Nephrology, The First Hospital of China Medical University, 
      Shenyang, China.
FAU - Yao, Li
AU  - Yao L
AD  - Department of Nephrology, The First Hospital of China Medical University, 
      Shenyang, China.
LA  - eng
PT  - Journal Article
DEP - 20220512
PL  - Switzerland
TA  - Front Oncol
JT  - Frontiers in oncology
JID - 101568867
PMC - PMC9133324
OTO - NOTNLM
OT  - CircSAFB2
OT  - M2 macrophage
OT  - exosome
OT  - miR-620/JAK1/STAT3
OT  - renal cell carcinoma
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/06/02 06:00
MHDA- 2022/06/02 06:01
PMCR- 2022/01/01
CRDT- 2022/06/01 11:39
PHST- 2021/11/04 00:00 [received]
PHST- 2022/04/06 00:00 [accepted]
PHST- 2022/06/01 11:39 [entrez]
PHST- 2022/06/02 06:00 [pubmed]
PHST- 2022/06/02 06:01 [medline]
PHST- 2022/01/01 00:00 [pmc-release]
AID - 10.3389/fonc.2022.808888 [doi]
PST - epublish
SO  - Front Oncol. 2022 May 12;12:808888. doi: 10.3389/fonc.2022.808888. eCollection 
      2022.