Oncotarget

Research Papers:

Let-7d increases ovarian cancer cell sensitivity to a genistein analog by targeting c-Myc

Ying-Xia Ning, Xin Luo, Meng Xu, Xin Feng and Jian Wang _

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Oncotarget. 2017; 8:74836-74845. https://doi.org/10.18632/oncotarget.20413

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Abstract

Ying-Xia Ning1,2,*, Xin Luo2, Meng Xu2,*, Xin Feng3,* and Jian Wang4

1Department of Gynaecology and Obstetrics, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China

2The First Affiliated Hospital of Jinan University, Guangzhou 510632, China

3Cancer Center, Traditional Chinese Medicine-Integrated Hospital, Southern Medical University, Guangzhou 510315, China

4Institute of Reproductive and Stem Cell Engineering, Central South University, National Engineering and Research Center of Human Stem Cell, Changsha, 41007, China

*These authors have contributed equally to this work

Correspondence to:

Jian Wang, email: 205106@csu.edu.cn

Xin Luo, email: tluox@126.com

Keywords: ovarian cancer, c-Myc, let-7d, genistein analogue, PI3K/AKT

Received: October 26, 2016    Accepted: June 02, 2017    Published: August 23, 2017

ABSTRACT

c-Myc is a key oncogenic transcription factor that participates in tumor pathogenesis. In this study, we found that levels of c-Myc mRNA and protein were higher in early ovarian cancer tissues than normal ovary samples. Increased c-Myc levels correlated positively with clinical stage I (Ia+b/Ic) in ovarian cancer patients. Patients with higher nuclear c-Myc expression had shorter overall survival times than patients with low c-Myc expression. Knocking down c-Myc sensitized ovarian cancer cells to 7-difluoromethoxyl-5,4’-di-n-octylgenistein (DFOG), a novel synthetic genistein analogue that suppressed PI3K/AKT signaling in vitro and in vivo. Finally, c-Myc was confirmed to be a direct target of let-7d, and let-7d-induced suppression of c-Myc increased the DFOG-sensitivity of ovarian cancer cells. These results indicate that nuclear c-Myc expression is an unfavorable factor in early ovarian cancer, and that let-7d increases ovarian cancer cell sensitivity to DFOG by suppressing c-Myc and PI3K/AKT signaling.


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