Breast cancer (BC) is the foremost cause of
cancer-related deaths in women. BC patients are oftentimes presented with
lymph node metastasis (LNM), which increases their risk of recurrence. Compelling data have recently implicated
microRNAs in promoting BC
metastasis. Therefore, the identification of
microRNA (
miRNA)-based molecular signature associated with LNM could provide an opportunity for a more personalized treatment for BC patients with high risk of LNM. In current study, we performed comprehensive
miRNA profiling in matched primary breast and LNM and identified 40
miRNAs, which were differentially expressed in LNM compared to primary
tumors. The expression of 14
miRNAs (Up: hsa-miR-155-5p, hsa-miR-150-5p, hsa-miR-146a-5p, hsa-miR-142-5p and down: hsa-miR-200a-3p, hsa-miR-200b-3p, hsa-miR-200c-3p, hsa-miR-205-5p, hsa-miR-210-3p, hsa-miR-214-3p, hsa-miR-141-3p, hsa-miR-127-3p, hsa-miR-125a-5p, and hsa-let-7c-5p) was subsequently validated in a second cohort of 32 breast and 32 matched LNM
tumor tissues. Mechanistically, forced expression of hsa-miR-205-5p, or hsa-miR-214-3p epigenetically inhibited MDA-MB-231 cell proliferation, colony formation, and cell migration. Global gene expression profiling on MDA-MB-231 cells overexpressing hsa-miR-205-5p, or hsa-miR-214-3p in combination with in silico target prediction and ingenuity pathway analyses identified multiple bona fide targets for hsa-miR-205-5p, hsa-miR-214-3p affecting cellular proliferation and migration. Interestingly, interrogation of the expression levels of hsa-miR-205 and
hsa-miR-214 in the METABRIC
breast cancer dataset revealed significantly poor overall survival in patients with downregulated expression of miR-205 [HR = 0.75 (0.61-0.91)], p = 0.003 and
hsa-miR-214 [HR = 0.74 (0.59-0.93) p = 0.008]. Our data unraveled the
miRNA-transcriptional landscape associated with LNM and provide novel insight on the role of several
miRNAs in promoting BC LNM, and suggest their potential utilization in the clinical management of BC patients.