Oncotarget

Research Papers:

Functional characterization of a novel transcript of ERCC1 in chemotherapy resistance of ovarian cancer

Jia Liu, Lin Zhang, Ping Mao, Guoqiang Jiang, Likun Liu, Jing Wang, Wei Yang, Lawrence Owusu and Weiling Li _

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Oncotarget. 2017; 8:85759-85771. https://doi.org/10.18632/oncotarget.20482

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Abstract

Jia Liu1,*, Lin Zhang2,*, Ping Mao3,*, Guoqiang Jiang1, Likun Liu1, Jing Wang1, Wei Yang4, Lawrence Owusu1,5 and Weiling Li1

1Department of Biotechnology, Dalian Medical University, Dalian, Liaoning, 116044, China

2Academy of Integrative Medicine, Dalian Medical University, Dalian, Liaoning, 116044, China

3Department of General Surgery, The People’s Hospital of Liaoning Province, Shenyang, Liaoning, 110016, China

4Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Sheng 450000, China

5Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, FL 33612, USA

*These authors have contributed equally to this work

Correspondence to:

Weiling Li, email: [email protected]

Keywords: larger ERCC1 transcript, cisplatin resistance, ovarian cancer, MAPK pathway

Received: April 23, 2017     Accepted: July 25, 2017     Published: August 24, 2017

ABSTRACT

Approximately 15-20% of ovarian cancer patients receiving platinum-based chemotherapy are primary platinum-resistant. Identification of these patients and transfer to other more effective therapy could reduce the morbidity of ovarian cancer. ERCC1 is a DNA repair gene which can complex with XPF to repair cisplatin-induced DNA damage and cause chemotherapy resistance. In this study, we found a novel ERCC1 transcript initiated upstream of the normal transcription initiation site. The expression of this larger ERCC1 transcript dramatically increased following cisplatin treatment in ovarian cancer cells and was regulated by the MAPK pathway. This phenomenon conferred enhanced cisplatin resistance on ovarian cancer cells, and was confirmed with chemosensitive and chemoresistant patients’ samples. Our data suggested that larger ERCC1 transcript levels correlated with the outcome of platinum-based chemotherapy.


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