PMID- 35443745
OWN - NLM
STAT- MEDLINE
DCOM- 20220422
LR  - 20221211
IS  - 2041-4889 (Electronic)
VI  - 13
IP  - 4
DP  - 2022 Apr 20
TI  - Exosomal miR-146a-5p and miR-155-5p promote CXCL12/CXCR7-induced metastasis of 
      colorectal cancer by crosstalk with cancer-associated fibroblasts.
PG  - 380
LID - 10.1038/s41419-022-04825-6 [doi]
LID - 380
AB  - C-X-C motif chemokine receptor 7 (CXCR7) is a newly discovered atypical chemokine 
      receptor that binds to C-X-C motif chemokine ligand 12 (CXCL12) with higher 
      affinity than CXCR4 and is associated with the metastasis of colorectal cancer 
      (CRC). Cancer-associated fibroblasts (CAFs) have been known to promote tumor 
      progression. However, whether CAFs are involved in CXCR7-mediated metastasis of 
      CRC remains elusive. We found a significant positive correlation between CXCR7 
      expression and CAF activation markers in colonic tissues from clinical specimens 
      and in villin-CXCR7 transgenic mice. RNA sequencing revealed a coordinated 
      increase in the levels of miR-146a-5p and miR-155-5p in CXCR7-overexpressing CRC 
      cells and their exosomes. Importantly, these CRC cell-derived miR-146a-5p and 
      miR-155-5p could be uptaken by CAFs via exosomes and promote the activation of 
      CAFs through JAK2-STAT3/NF-kappaB signaling by targeting suppressor of cytokine 
      signaling 1 (SOCS1) and zinc finger and BTB domain containing 2 (ZBTB2). 
      Reciprocally, activated CAFs further potently enhanced the invasive capacity of 
      CRC cells. Mechanistically, CAFs transfected with miR-146a-5p and miR-155-5p 
      exhibited a robust increase in the levels of inflammatory cytokines 
      interleukin-6, tumor necrosis factor-alpha, transforming growth factor-beta, and CXCL12, 
      which trigger the epithelial-mesenchymal transition and pro-metastatic switch of 
      CRC cells. More importantly, the activation of CAFs by miR-146a-5p and miR-155-5p 
      facilitated tumor formation and lung metastasis of CRC in vivo using tumor 
      xenograft models. Our work provides novel insights into CXCR7-mediated CRC 
      metastasis from tumor-stroma interaction and serum exosomal miR-146a-5p and 
      miR-155-5p could serve as potential biomarkers and therapeutic targets for 
      inhibiting CRC metastasis.
CI  - (c) 2022. The Author(s).
FAU - Wang, Dong
AU  - Wang D
AD  - Department of Pharmacology, School of Basic Medical Sciences, Capital Medical 
      University, Beijing, China.
FAU - Wang, Xiaohui
AU  - Wang X
AD  - Department of General Surgery, Xuanwu Hospital, Capital Medical University, 
      Beijing, China.
FAU - Song, Yujia
AU  - Song Y
AD  - Department of Pharmacology, School of Basic Medical Sciences, Capital Medical 
      University, Beijing, China.
FAU - Si, Mahan
AU  - Si M
AD  - Department of Pharmacology, School of Basic Medical Sciences, Capital Medical 
      University, Beijing, China.
FAU - Sun, Yuqi
AU  - Sun Y
AD  - Department of Pharmacology, School of Basic Medical Sciences, Capital Medical 
      University, Beijing, China.
FAU - Liu, Xiaohui
AU  - Liu X
AD  - Department of Pharmacology, School of Basic Medical Sciences, Capital Medical 
      University, Beijing, China.
FAU - Cui, Shuxiang
AU  - Cui S
AUID- ORCID: 0000-0002-4466-6045
AD  - Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital 
      Medical University, Beijing, China.
FAU - Qu, Xianjun
AU  - Qu X
AD  - Department of Pharmacology, School of Basic Medical Sciences, Capital Medical 
      University, Beijing, China.
FAU - Yu, Xinfeng
AU  - Yu X
AUID- ORCID: 0000-0002-2703-4361
AD  - Department of Pharmacology, School of Basic Medical Sciences, Capital Medical 
      University, Beijing, China. xyu@ccmu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220420
PL  - England
TA  - Cell Death Dis
JT  - Cell death & disease
JID - 101524092
RN  - 0 (CXCL12 protein, human)
RN  - 0 (Chemokine CXCL12)
RN  - 0 (MIRN155 microRNA, human)
RN  - 0 (MicroRNAs)
RN  - 0 (Mirn155 microRNA, mouse)
RN  - 0 (Repressor Proteins)
RN  - 0 (ZBTB2 protein, human)
SB  - IM
MH  - Animals
MH  - *Cancer-Associated Fibroblasts/metabolism
MH  - Cell Line, Tumor
MH  - Cell Proliferation/genetics
MH  - Chemokine CXCL12/genetics/metabolism
MH  - *Colorectal Neoplasms/pathology
MH  - *Exosomes/metabolism
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Mice
MH  - *MicroRNAs/genetics/metabolism
MH  - Repressor Proteins/metabolism
PMC - PMC9021302
COIS- The authors declare no competing interests.
EDAT- 2022/04/22 06:00
MHDA- 2022/04/23 06:00
PMCR- 2022/04/20
CRDT- 2022/04/21 05:14
PHST- 2021/09/06 00:00 [received]
PHST- 2022/04/04 00:00 [accepted]
PHST- 2022/03/29 00:00 [revised]
PHST- 2022/04/21 05:14 [entrez]
PHST- 2022/04/22 06:00 [pubmed]
PHST- 2022/04/23 06:00 [medline]
PHST- 2022/04/20 00:00 [pmc-release]
AID - 10.1038/s41419-022-04825-6 [pii]
AID - 4825 [pii]
AID - 10.1038/s41419-022-04825-6 [doi]
PST - epublish
SO  - Cell Death Dis. 2022 Apr 20;13(4):380. doi: 10.1038/s41419-022-04825-6.