Urokinase-type plasminogen activator receptor inhibits apoptosis in triple-negative breast cancer through miR-17/20a suppression of death receptors 4 and 5
Year: 2017
Type: article
Abstract: // Xin Li 1, * , Bo Wu 1, * , Lizhao Chen 1 , Ying Ju 1 , Changfei Li 1 and Songdong Meng 1, 2 1 CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing, China 2 College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China * These authors have contributed equally to this work Correspondence to: Songdong Meng, email: [email protected] Changfei Li, email: [email protected] Keywords: uPAR,miR-17-5p, miR-20a, DR5, apoptosis Received: December 21, 2016 Accepted: July 23, 2017 Published: August 24, 2017 ABSTRACT 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 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.
Source: Oncotarget
Authors: Xin Li, Bo Wu, Lizhao Chen, Ying Ju, Changfei Li, Songdong Meng
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: diamond
OpenAlex ID: W2745867083