Melatonin Regulates Breast Cancer Progression by the lnc010561/miR-30/FKBP3 Axis

Peng Liu; Xinhua Xie; Anli Yang; Yanan Kong; Diane Allen-Gipson; Zhi Tian; Liye Zhou; Hailin Tang; Xiaoming Xie

doi:10.1016/j.omtn.2019.12.019

Melatonin Regulates Breast Cancer Progression by the lnc010561/miR-30/FKBP3 Axis

Mol Ther Nucleic Acids. 2020 Mar 6:19:765-774. doi: 10.1016/j.omtn.2019.12.019. Epub 2019 Dec 24.

Authors

Peng Liu¹, Xinhua Xie¹, Anli Yang¹, Yanan Kong¹, Diane Allen-Gipson², Zhi Tian², Liye Zhou³, Hailin Tang⁴, Xiaoming Xie⁵

Affiliations

¹ Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
² Colleges of Pharmacy, University of South Florida, Tampa, FL, USA.
³ Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
⁴ Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China. Electronic address: tanghl@sysucc.org.cn.
⁵ Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China. Electronic address: xiexm@sysucc.org.cn.

Abstract

Melatonin has been recognized to slow breast cancer growth. The molecular mechanisms may involve long non-coding RNAs (lncRNAs). However, little is known on how melatonin affects lncRNA expression and function in breast cancer. We used microarrays to explore the expression profile of mRNAs and lncRNAs in melatonin-treated breast cancer cells. Kyoto encyclopedia of genes and genomes (KEGG) and Reactome pathways analysis were performed to identify the signaling pathways affected by altered expressed mRNAs after melatonin treatment. To explore the functions and mechanisms of the selected differentially expressed mRNA and lncRNA in breast cancer, we performed a series of experiments. We found that FK506-binding protein 3 (FKBP3) and lnc010561 were downregulated in melatonin-treated breast cancer cells. Knockdown of FKBP3 and lnc010561 inhibited breast cancer proliferation and invasion, and induced apoptosis. Also, lnc010561 and FKBP3 functioned as competing endogenous RNAs (ceRNAs) for miR-30. Our findings suggested that melatonin regulated breast cancer progression by the lnc010561/miR-30/FKBP3 axis. Melatonin may, therefore, function as an anticancer strategy for breast cancer.

Keywords: FKBP3; breast cancer; lncRNA; melatonin; miR-30.