Mirna-490-3p Promotes The Metastatic Progression Of Invasive Ductal Carcinoma

MicroRNA (miRNA/mir)-490-3p has been defined as a tumor suppressor in different types of cancer, including breast cancer. However, miR-490-3p has been shown to function as a tumor suppressor and promoter in a context-dependent manner in hepatocellular and lung cancer. Contrary to previous studies, the present study revealed that miR-490-3p expression was significantly higher in invasive ductal carcinoma (IDC) tissue specimens, the most common form of breast cancer, compared to tumor-adjacent normal tissue specimens (n=20). Its expression was also higher in the more metastatic breast cancer cell line, MDA-MB-231, compared to the non-metastatic breast cancer cell line, MCF7, and the moderately metastatic breast cancer cell line, MDA-MB-468. The expression of miR-490-3p was induced following transforming growth factor (TGF)-beta-induced epithelial-to-mesenchymal transition (EMT) in MCF10A cells. Gain-and loss-of-function assays revealed that the expression of miR-490-3p regulated the proliferation, colony formation, EMT, migration and invasion in vitro, but not the apoptosis of MDA-MB-468 and MDA-MB-231 cells. The knockdown of miR-490-3p expression in MDA-MB-231 cells inhibited experimental metastasis in a tumor xenograft assay. As in lung cancer, miR-490-3p was found to target and downregulate the expression of the tumor suppressor RNA binding protein poly r(C) binding protein 1 (PCBP1). PCBP1 protein and miR-490-3p expression inversely correlated in patients with ductal carcinoma in situ (DCIS; n=10; no nodal involvement) and IDC (n=10; different stages of metastatic progression) with a significantly higher miR-490-3p expression in patients with IDC compared to those with DCIS. The expression of miR-490-3p was negatively associated with both overall and disease-free survival in the patients with breast cancer included in the present study. On the whole, the results confirm a pro-metastatic role of miR-490-3p in IDC, establishing it as a biomarker for disease progression in these patients.