miR-187 Is an Independent Prognostic Factor in Breast Cancer and Confers Increased Invasive PotentialIn Vitro

Abstract

Purpose: Here, we describe an integrated bioinformatics, functional analysis, and translational pathology approach to identify novel miRNAs involved in breast cancer progression.Experimental Design: Coinertia analysis (CIA) was used to combine a database of predicted miRNA target sites and gene expression data. Using two independent breast cancer cohorts, CIA was combined with correspondence analysis and between group analysis to produce a ranked list of miRNAs associated with disease progression. Ectopic expression studies were carried out in MCF7 cells and miRNA expression evaluated in two additional cohorts of patients with breast cancer by in situ hybridization on tissue microarrays.Results: CIA identified miR-187 as a key miRNA associated with poor outcome in breast cancer. Ectopic expression of miR-187 in breast cancer cells resulted in a more aggressive phenotype. In a test cohort (n ¼ 117), high expression of miR-187 was associated with a trend toward reduced breast cancer-specific survival (BCSS; P ¼ 0.058), and a significant association with reduced BCSS in lymph node-positive patients (P ¼ 0.036). In a validation cohort (n ¼ 470), high miR-187 was significantly associated with reduced BCSS in the entire cohort (P ¼ 0.021) and in lymph node-positive patients (P ¼ 0.012). Multivariate Cox regression analysis revealed that miR-187 is an independent prognostic factor in both cohorts [cohort 1: HR, 7.37; 95% confidence interval (CI), 2.05-26.51; P ¼ 0.002; cohort 2: HR, 2.80; 95% CI, 1.52-5.16; P ¼ 0.001] and in lymph node-positive patients in both cohorts (cohort 1: HR, 13.74; 95% CI, 2.62-72.03; P ¼ 0.002; cohort 2: HR, 2.77; 95% CI, 1.32-5.81; P ¼ 0.007).Conclusions: miR-187 expression in breast cancer leads to a more aggressive, invasive phenotype and acts as an independent predictor of outcome. Clin Cancer Res; 18(24); 6702-13. Ó2012 AACR.

MicroRNA-187 induces diffuse large B-cell lymphoma cell apoptosis via targeting BCL6

“…Studies have implicated miR-187 activity in the development of various types of tumors (5,17,18); however, its role in DLBCL has not yet been established.…”

Low MiR-187 Expression Promotes Resistance to Chemoradiation Therapy In Vitro and Correlates with Treatment Failure in Patients with Esophageal Adenocarcinoma

“…Kim and colleagues previously demonstrated that miR-187 is decreased in taxol-resistant ovarian cell lines (29), supporting the data presented here. However, in breast cancer cells, miR-187 was demonstrated to have no effect on sensitivity to tamoxifen or fulvestrant (30). These conflicting data may be due to the tumor-and/or tissue-specific function of miR-187 or may result from the differing modes of action of these cytotoxic agents.…”

Noncoding RNAs in breast cancer

“…Expression levels of a number of miRNAs, which are either positively or inversely associated with metastatic status, disease-free time and overall survival of breast cancer patients have been identified [225][226][227][228][229][230][231][232][233][234][235][236][237][238][239][240] and are detailed in Table 3. The most relevant miRNA with prognostic value in breast cancer is miR-210, the aforementioned oncogenic miRNA implicated in the DCIS-to-IDC transition.…”