Abstract 3560: MicroRNA-665 promotes metastasis of breast cancer by targeting nuclear receptor subfamily 4 group A member 3

Abstract

Abstract Background: It is the result of metastasis to the lymph nodes or other organs that leads breast cancer (BC) patients to death. Then the early detection of metastasis in BC is helpful to regulate progression of BC and then predict prognosis of BC patients. Since the abnormal level of miRNAs are bound up with BC and metastasis, of which may act as biomarkers to predict prognosis of BC, we find that expression level of miR-665 is ectopic up-regulated in BC patients and it may serve as an estimable biomarker of prognosis of BC patients. Methods: The expressions of miRNA were detected by our current microarray system and verified by quantitative real-time reverse transcription-PCR (qRT-PCR). In Student’s t-test and Kaplan-Meier analysis, the levels of miR-665 were positively correlated with poor survival in BC patients. Multivariate survival analysis identified either miR-665 expression or TNM stage as an independent prognostic factor of BC. Diverse roles of miR-665 played in various cellular functions were examined by loss-of-function and gain-of-function effects in vitro and in vivo. Dual-luciferase reporter gene experiment was then used to confirm the direct complementation between miR-665 and NR4A3, accompanied by activating the epithelial-mesenchymal transition (EMT). Furthermore, siRNAs targeting NR4A3 were used to rescue cell migration and invasion in miR-665 knockdown cells. Results: Expression of miR-665 was upregulated which predicted poor prognosis in BC patients. Since miR-665 may regulate key processes of tumorigenesis, targeting of NR4A3 was proved to promote cell migration and invasion by activating the EMT. Accordingly, either silencing of miR-665 or over-expressing of NR4A3 rescued the migration and invasion phenotype in vitro. Conclusions: Our study suggests that miR-665 plays an important part in progression of BC and promotes cell migration as well as invasion by down-regulation of NR4A3. The data collectively indicate that miR-665 is an onco-miRNA and may represents a potential predictor for diagnosis and prognosis of BC. Citation Format: Xinge Zhao. MicroRNA-665 promotes metastasis of breast cancer by targeting nuclear receptor subfamily 4 group A member 3 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3560.