PMID- 29179464
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220330
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 8
IP  - 51
DP  - 2017 Oct 24
TI  - Urokinase-type plasminogen activator receptor inhibits apoptosis in 
      triple-negative breast cancer through miR-17/20a suppression of death receptors 4 
      and 5.
PG  - 88645-88657
LID - 10.18632/oncotarget.20435 [doi]
AB  - Dissection and understanding of the molecular pathways driving triple-negative 
      breast cancer (TNBC) are urgently needed to develop efficient tailored therapies. 
      Aside from cell invasion and metastasis, the urokinase-type plasminogen activator 
      receptor (uPAR) has been linked to apoptosis resistance in breast tumors. We 
      explored the mechanism of uPAR-disrupted apoptosis in breast cancer. We found 
      that depletion of uPAR by RNAi increases death receptor 4 (DR4) and death 
      receptor 5 (DR5) expression and triggers TRAIL-induced apoptosis in TNBC cells. 
      The microRNAs miR-17-5p and miR-20a inhibit cell apoptosis via suppression of 
      DR4/DR5. We provide evidence that uPAR enhances miR-17-5p/20a expression through 
      upregulation of c-myc. Blocking miR-17-5p/20a with antagomiRNA suppressed the 
      growth of uPAR-overexpressing breast tumor xenografts in mice. These results 
      indicate that uPAR suppresses cell apoptosis by inhibiting the 
      c-myc-miR-17/5p/20a-DR4/DR5 pathway. Therapy directed at uPAR-induced miR-17/20a 
      is a potential option for breast cancer and TNBC.
FAU - Li, Xin
AU  - Li X
AD  - CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of 
      Microbiology, Chinese Academy of Sciences (CAS), Beijing, China.
FAU - Wu, Bo
AU  - Wu B
AD  - CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of 
      Microbiology, Chinese Academy of Sciences (CAS), Beijing, China.
FAU - Chen, Lizhao
AU  - Chen L
AD  - CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of 
      Microbiology, Chinese Academy of Sciences (CAS), Beijing, China.
FAU - Ju, Ying
AU  - Ju Y
AD  - CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of 
      Microbiology, Chinese Academy of Sciences (CAS), Beijing, China.
FAU - Li, Changfei
AU  - Li C
AD  - CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of 
      Microbiology, Chinese Academy of Sciences (CAS), Beijing, China.
FAU - Meng, Songdong
AU  - Meng S
AD  - CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of 
      Microbiology, Chinese Academy of Sciences (CAS), Beijing, China.
AD  - College of Life Sciences, University of Chinese Academy of Sciences, Beijing, 
      China.
LA  - eng
PT  - Journal Article
DEP - 20170824
PL  - United States
TA  - Oncotarget
JT  - Oncotarget
JID - 101532965
PMC - PMC5687634
OTO - NOTNLM
OT  - DR5
OT  - apoptosis
OT  - miR-17-5p
OT  - miR-20a
OT  - uPAR
COIS- CONFLICTS OF INTEREST No potential conflicts of interest were disclosed.
EDAT- 2017/11/29 06:00
MHDA- 2017/11/29 06:01
PMCR- 2017/10/24
CRDT- 2017/11/29 06:00
PHST- 2016/12/21 00:00 [received]
PHST- 2017/07/23 00:00 [accepted]
PHST- 2017/11/29 06:00 [entrez]
PHST- 2017/11/29 06:00 [pubmed]
PHST- 2017/11/29 06:01 [medline]
PHST- 2017/10/24 00:00 [pmc-release]
AID - 20435 [pii]
AID - 10.18632/oncotarget.20435 [doi]
PST - epublish
SO  - Oncotarget. 2017 Aug 24;8(51):88645-88657. doi: 10.18632/oncotarget.20435. 
      eCollection 2017 Oct 24.