Abstract 3439: MicroRNA-34a epigenetically silences epithelial-mesenchymal transitions (EMT)-TFs in metastatic breast cancer cells

Abstract

Abstract MicroRNA-34a (miR-34a) as key regulator of tumor suppression gene potentially plays a profound role in the tumorigenesis and progression of several cancers including breast cancer. In the present study, we invstigated the expression, targets and functional effects of miR-34a and its correlation with tumour characteristics and clinical outcome in the epithelial to mesenchymal transitions (EMT) stage of metastatic breast cancer (MBC). We focused to analyze EMT-inducing transcription factors (EMT-TFs)/miR-34a feedback loop, like TWIST1, SLUG, ZEB1/2, NOTCH1, on promotes MBC migration, invasion and metastasis. We found that miR-34a potently inhibits NOTCH1, ZEB1 protein expression activity in breast cancer cells. Importantly, the miR-34a do not have any inhibitory effects upon the SLUG and ZEB2. Using quantitative reverse transcription-PCR and western blot analysis, we showed that average pre-miR-34a expression is down regulated in human metastatic breast tissues as compared to normal human breast and negatively correlates with clinicopathological features of MBC patients. Ectopic expression of miR-34a in metastatic breast cancer cell-line BT-549 significantly inhibited cell proliferation, migrations, survival and cell invasion, but no clear effect on cancer cell growth. We provide indication that these regulatory pathways may stabilize epithelial and mesenchymal states, individually. We have consequently revealed that miR-34a is downregulated in MBC tissues and that it suppresses tumor growth by affecting several malignancy endpoints via downregulation of multiple EMT-TFs. Mutational or epigenetic inactivation of the EMT-TFs/miR-34a pathway probably alterations the equilibrium of these regulations toward EMT and the mesenchymal state and thereby contributes to metastasis. The results also suggest that miR-34a could serve as a potential therapeutic agent for MBC. Funding support: This work was supported by the NSFC (81172049, 81672887), Corresponding author email:fujunjiang@hotmail.com;fujunjiang@swmu.edu.cn Citation Format: Saber Imani, Chunli Wei, Jingliang Cheng, Junjiang Fu. MicroRNA-34a epigenetically silences epithelial-mesenchymal transitions (EMT)-TFs in metastatic breast cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3439. doi:10.1158/1538-7445.AM2017-3439