MicroRNA-9 as Potential Biomarker for Breast Cancer Local Recurrence and Tumor Estrogen Receptor Status

Abstract

MicroRNAs (miRs) are small, non-protein coding transcripts involved in many cellular functions. Many miRs have emerged as important cancer biomarkers. In the present study, we investigated whether miR levels in breast tumors are predictive of breast cancer local recurrence (LR). Sixty-eight women who were diagnosed with breast cancer at the Lombardi Comprehensive Cancer Center were included in this study. Breast cancer patients with LR and those without LR were matched on year of surgery, age at diagnosis, and type of surgery. Candidate miRs were identified by screening the expression levels of 754 human miRs using miR arrays in 16 breast tumor samples from 8 cases with LR and 8 cases without LR. Eight candidate miRs that showed significant differences between tumors with and without LR were further verified in 52 tumor samples using real-time PCR. Higher expression of miR-9 was significantly associated with breast cancer LR in all cases as well as the subset of estrogen receptor (ER) positive cases (p = 0.02). The AUCs (Area Under Curve) of receiver operating characteristic (ROC) curves of miR-9 for all tumors and ER positive tumors are 0.68 (p = 0.02) and 0.69 (p = 0.02), respectively. In ER positive cases, Kaplan-Meier analysis showed that patients with lower miR-9 levels had significantly better 10-year LR-free survival (67.9% vs 30.8%, p = 0.02). Expression levels of miR-9 and another miR candidate, miR-375, were also strongly associated with ER status (p<0.001 for both). The potential of miR-9 as a biomarker for LR warrants further investigation with larger sample size.

Grouping miRNAs of similar functions via weighted information content of gene ontology

“…In fact, recent research shows that miRNA-9 is a potential biomarker for breast cancer [30]. The miRNA-129 is also predicted as a regulator in breast cancer by our method.…”

LncRNA Taurine-Upregulated Gene 1 Promotes Cell Proliferation by Inhibiting MicroRNA-9 in MCF-7 Cells

“…MiR-9 was found to be upregulated in tumors with aggressive phenotypes, and its upregulated has been linked to the poor prognosis of breast cancer [15]. Zhou et al [25] reported that higher expression of miR-9 is significantly associated with local recurrence of breast cancer in patients with a positive tumor estrogen receptor status. As one of the identified targets of miR-9, MTHFD2, regulated by miR-9, contributes to the anti-proliferative activity of miR-9 in breast cancer [26].…”

Post-transcriptional Regulation of Human Breast Cancer Cell Proteome by Unliganded Estrogen Receptor β via microRNAs

“…Their downregulation by ER␤, together with that of miR-10b (69,70), suggests a potential mechanism for the low metastatic potential of BC cells expressing this ER subtype. Among the miRNAs down-regulated by ER␤, miR-221 and miR-222 were identified as basal-like cell-specific miRNAs and were shown to function as regulators of epithelial-to-mesenchymal transition, with high expression in luminal-like BC cells resulting in increased cell migration and invasion due to the regulation of mesenchymal-specific genes (71), whereas low miR-9 expression has been associated with a less aggressive BC phenotype (72). The up-regulated miR-125b, in contrast, has been found down-regulated in HER2-overexpressing BCs (73) and is able to suppress HER2 and HER3 mRNA and protein levels, leading to a reduction in anchorage-dependent cell growth, motility, and invasiveness (74).…”