J Cancer 2019; 10(2):547-555. doi:10.7150/jca.27748

Research Paper

MicroRNA-449a Inhibits Tumor Metastasis through AKT/ERK1/2 Inactivation by Targeting Steroid Receptor Coactivator (SRC) in Endometrial Cancer

Yuan Hu1,2,*, An-Yue Wu1,2,*, Cong Xu1,2, Ke-Qi Song1,2, Wen-Jing Wang1,2, Xia Yin1,2, Wen Di1,2,3, Zu-Bei Hong1,2,✉, Li-Hua Qiu1,2,✉

1. Department of Obstetrics and Gynecology, Ren Ji Hospital, School of Medicine, Shanghai JiaoTong University, Shanghai 200127, China
2. Shanghai Key Laboratory of Gynecologic Oncology, Shanghai 200127, China
3. State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University
* Co-first authors: these authors contributed equally to this work.

Abstract

Endometrial cancer represents the leading frequency in gynecological malignancy in developed countries. Even with early detection, metastasis and recurrence remain the main reasons for a high death rate. MicroRNA-449a (miR-449a) has been reported to function as a tumor suppressor, yet the role of miR-449a in endometrial cancer metastasis has not been investigated. The present study identified that miR-449a was downregulated in advanced endometrial cancer. Overexpression of miR-449a decreased the migration and invasion of KLE and AN3CA endometrial cancer cells. Using luciferase reporter assays, we identified that miR-449a directly targeted the steroid receptor coactivator (SRC) by binding to sites in the 3ʹ untranslated regions. Elevated expressions of SRC have been witnessed in advanced endometrial cancer tissues and have promoted tumor metastasis. We also identified that the suppressive effect of miR-449a on metastasis could be mediated by downregulating SRC and that miR-449a could suppress AKT and ERK1/2 pathway activation in endometrial cancer cells. These findings contribute to the current understanding of the function of miR-449a in endometrial cancer.

Keywords: Endometrial cancer, MicroRNA-449a, SRC, Metastasis

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How to cite this article:
Hu Y, Wu AY, Xu C, Song KQ, Wang WJ, Yin X, Di W, Hong ZB, Qiu LH. MicroRNA-449a Inhibits Tumor Metastasis through AKT/ERK1/2 Inactivation by Targeting Steroid Receptor Coactivator (SRC) in Endometrial Cancer. J Cancer 2019; 10(2):547-555. doi:10.7150/jca.27748. Available from http://www.jcancer.org/v10p0547.htm