Post-transcriptional up-regulation of PDGF-C by HuR in advanced and stressed breast cancer.
Breast cancer is a heterogeneous disease characterized by multiple genetic alterations leading to the activation of growth factor signaling pathways that promote cell proliferation. Platelet-derived growth factor-C (PDGF-C) is overexpressed in various malignancies; however, the involvement of PDGF-C in breast cancers and the mechanisms underlying PDGF-C deregulation remain unclear. Here, we show that PDGF-C is overexpressed in clinical breast cancers and correlates with poor prognosis. PDGF-C up-regulation was mediated by the human embryonic lethal abnormal vision-like protein HuR, which stabilizes the PDGF-C transcript by binding to two predicted AU-rich elements (AREs) in the 3'-untranslated region (3'-UTR). HuR is up-regulated in hydrogen peroxide-treated or ultraviolet-irradiated breast cancer cells. Clinically, HuR levels are correlated with PDGF-C expression and histological grade or pathological tumor-node-metastasis (pTNM) stage. Our findings reveal a novel mechanism underlying HuR-mediated breast cancer progression, and suggest that HuR and PDGF-C are potential molecular candidates for targeted therapy of breast cancers.
Department of General Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an 710032, China. lna2012@fmmu.edu.cn.
Nian-An
NA
Luo
Department of General Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an 710032, China. 604829845@163.com.
Ya-Qi
YQ
Qu
Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi'an 710032, China. guodong.yang029@gmail.com.
Guo-Dong
GD
Yang
Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi'an 710032, China. wangt78@fmmu.edu.cn.
Tao
T
Wang
Department of General Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an 710032, China. liren_li_ok@126.com.
Ren-Li
RL
Li
Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi'an 710032, China. jialth@fmmu.edu.cn.
Lin-Tao
LT
Jia
Department of General Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an 710032, China. dongrui@fmmu.edu.cn.
Rui
R
Dong
D020413:3' Untranslated Regions / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D045744:Cell Line, Tumor; D051959:ELAV Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008222:Lymphokines / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009367:Neoplasm Staging; D010982:Platelet-Derived Growth Factor / Q000235:genetics* / Q000378:metabolism; D011379:Prognosis; D020871:RNA Stability / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013312:Stress, Physiological; D014158:Transcription, Genetic; D015854:Up-Regulation / Q000235:genetics*
D020413:3' Untranslated Regions; D051959:ELAV Proteins; D008222:Lymphokines; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; C411423:platelet-derived growth factor C