MicroRNA-200c and microRNA- 141 are regulated by a FOXP3-KAT2B axis and associated with tumor metastasis in breast cancer

Abstract

BackgroundMembers of the microRNA (miR)-200 family, which are involved in tumor metastasis, have potential as cancer biomarkers, but their regulatory mechanisms remain elusive.MethodsWe investigated FOXP3-inducible breast cancer cells, Foxp3 heterozygous Scurfy mutant (Foxp3 sf/+) female mice, and patients with breast cancer for characterization of the formation and regulation of the miR-200 family in breast cancer cells and circulation. Participants (259), including patients with breast cancer or benign breast tumors, members of breast cancer families, and healthy controls, were assessed for tumor and circulating levels of the miR-200 family.ResultsFirst, we identified a FOXP3-KAT2B-miR-200c/141 axis in breast cancer cells. Second, aging Foxp3 sf/+ female mice developed spontaneous breast cancers and lung metastases. Levels of miR-200c and miR-141 were lower in Foxp3 sf/+ tumor cells than in normal breast epithelial cells, but plasma levels of miR-200c and miR-141 in the Foxp3 sf/+ mice increased during tumor progression and metastasis. Third, in patients with breast cancer, the levels of miR-200c and 141 were lower in FOXP3 low relative to those with FOXP3 high breast cancer cells, especially in late-stage and metastatic cancer cells. The levels of miR-200c and miR-141 were higher in plasma from patients with metastatic breast cancer than in plasma from those with localized breast cancer, with benign breast tumors, with a family history of breast cancer, or from healthy controls. Finally, in Foxp3 sf/+ mice, plasma miR-200c and miR-141 appeared to be released from tumor cells.ConclusionsmiR-200c and miR-141 are regulated by a FOXP3-KAT2B axis in breast cancer cells, and circulating levels of miR-200c and miR-141 are potential biomarkers for early detection of breast cancer metastases.Electronic supplementary materialThe online version of this article (doi:10.1186/s13058-017-0858-x) contains supplementary material, which is available to authorized users.

Breast cancer diagnosis: Imaging techniques and biochemical markers

“…In a study, Zhang et al (2017) could be used as diagnostic biomarkers for detection patients with early stage of breast cancer metastasis (Zhang et al, 2017).…”

Identification of miRNAs Enriched in Extracellular Vesicles Derived from Serum Samples of Breast Cancer Patients

“…Several studies have suggested that miRNAs could be suitable biomarkers [12][13][14][15] for early diagnosis of cancer, notably for its remarkable stability in liquid biopsies. In this context, although in its early stages, the use of EV-derived miRNAs (EV-miRNAs) from serum and plasma as a biomarker for BC have shown promising results [7,14,[16][17][18][19]. Among the EV-miRNAs described to be overexpressed in BC compared to control are miR-21, miR-1246 [7], and the miR-106a-363 cluster [14].…”

MicroRNA-223 Targeting STIM1 Inhibits the Biological Behavior of Breast Cancer

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