miR-16 enhances miR-302/367-induced reprogramming and tumor suppression in breast cancer cells.

Overexpression of either miR-302 or miR-302/367 cluster induces reprogramming of cancer cells and exerts tumor-suppressive effects by induction of mesenchymal-to-epithelial transition, apoptosis and a less proliferative capacity. Several reports have described miR-16 as a tumor suppressor microRNA (miRNA). Here, we studied the impact of exogenous induction of miR-16 in MDA-MB-231 and SK-BR-3 breast cancer cells following overexpression of miR-302/367 cluster and investigated whether transfection of these cells by a mature miR-16 mimic could affect the reprogramming state of the cells and their tumorigenicity. miR-16 enhanced the expression levels of OCT4A, SOX2, and NANOG, generally known as transcription or pluripotency factors, and suppressed proliferation and invasiveness of these cells. Meanwhile, inhibition of miR-16 counteracted both the reprogramming effect and the antitumor function of miR-302/367 in the breast cancer cells. Current results indicate that miR-16 can work as an adjuvant to improve both cancer cell reprogramming and tumor-suppressive function of miR-302/367 cluster in MDA-MB-231 and SK-BR-3 cells, while its inhibition counteracts all of these effects. Combined application of miRNAs that share some common targets in cancer cell signaling pathways may provide new approaches for repression of multiple hallmarks of cancer.