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Int. J. Mol. Sci. 2014, 15(11), 20306-20320; doi:10.3390/ijms151120306

Post-Transcriptional Up-Regulation of PDGF-C by HuR in Advanced and Stressed Breast Cancer

1
Department of General Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an 710032, China
2
Department of General Surgery, 10 Hospital of People's Liberation Army (PLA), Wuwei 733000, China
3
Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi'an 710032, China
These authors contributed equally to this work.
*
Authors to whom correspondence should be addressed.
Received: 11 August 2014 / Revised: 16 October 2014 / Accepted: 28 October 2014 / Published: 6 November 2014
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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Abstract

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. View Full-Text
Keywords: breast neoplasms; HuR; mRNA stability; platelet-derived growth factor-C (PDGF-C) breast neoplasms; HuR; mRNA stability; platelet-derived growth factor-C (PDGF-C)
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Luo, N.-A.; Qu, Y.-Q.; Yang, G.-D.; Wang, T.; Li, R.-L.; Jia, L.-T.; Dong, R. Post-Transcriptional Up-Regulation of PDGF-C by HuR in Advanced and Stressed Breast Cancer. Int. J. Mol. Sci. 2014, 15, 20306-20320.

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