Abstract 5446: Tumor-derived miR-200c and 141 contribute to high levels of plasma microRNA-200c and 141 through exosomes

Abstract

Abstract Circulating microRNAs (miRs) have potential as cancer biomarkers, but their regulatory mechanisms remain elusive. Here we used a breast cancer model (Foxp3 heterozygous Scurfy mutant female mice, Foxp3sf/+) for identification of circulating miR biomarkers, and the formation and regulation of these miRs were investigated. Aging Foxp3sf/+ female mice developed spontaneous breast cancers and lung metastases. Levels of miR-200c and 141 were lower in the Foxp3sf/+ breast cancer cells than in normal breast epithelial cells, but plasma levels of miR-200c and 141 in the Foxp3sf/+ mice increased during tumor progression, especially during metastasis to the lung. Likewise, 259 participants, including patients with breast cancer or benign breast tumors, members of breast cancer families, and matched normal healthy controls, were assessed for circulating levels of candidate miRs. The results showed that: 1) the levels of miR-200c and 141 were lower in the FOXP3low breast cancer cells relative to those with FOXP3high, especially for late-stage and metastatic cancer cells; 2) the levels of miR-200c and 141 were higher in plasma of patients with metastatic breast cancer than in plasma of those with localized breast cancer, with benign breast tumors, with a family history of breast cancer, or normal healthy controls. Furthermore, in Foxp3sf/+ mice, plasma miR-200c and 141 were released from tumor cells through exosomes. Thus, plasma levels of miR-200c and 141 are potential biomarkers for early detection of metastases. MiR-200c and 141 appear to be released from breast cancer cells, through exosomes, into the circulation. Citation Format: Lizhong Wang, Runhua Liu, Song Gao, Yicun Wang, Meng Wang, Zhi Li. Tumor-derived miR-200c and 141 contribute to high levels of plasma microRNA-200c and 141 through exosomes [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 5446. doi:10.1158/1538-7445.AM2017-5446