Fig. 4.

miR-148a-3p, miR-148b-3p and miR-152-3p directly targeted SPIN1 and increased chemosensitivity in breast cancer cells. a The 3’-UTR element of SPIN1 mRNA is partially complementary to miR-148a-3p, miR-148b-3p and miR-152-3p. b The relative luciferase activity was significantly reduced in the miR-148a/148b/152-3p overexpressing cells (^*P < 0.05) and these effects could be abolished by mutation of SPIN1 3’-UTR. c-d The SPIN1 protein expression was clearly reduced after the transfection of miR-148a-3p, miR-148b-3p or miR-152-3p. e The expression levels of miR-148a-3p, miR-148b-3p and miR-152-3p were lower in MCF-7/ADM cells than that in MCF-7 cells. f-g Transfection of miR-148a-3p, miR-148b-3p, miR-152-3p, or cotransfection of these three miRNAs significantly increased the miRNAs levels. h-i miR-148a-3p, miR-148b-3p and miR-152-3p decreased Adriamycin resistance in MCF-7/ADM and MCF-7 cells. In MCF-7 cells, miR-148a-3p or miR-152-3p (Adriamycin = 0.1 μM and 1 μM), and miR-152-3p (Adriamycin = 10 μM) could significantly reduce cell viability, compared with the negative control (NC) group (*P < 0.05, t-test). In MCF-7/ADM cells, miR-148a-3p or miR-152-3p (Adriamycin = 0.1 μM), and miR-148a-3p, miR-148b-3p or miR-152-3p (Adriamycin = 1 μM and 10 μM) could significantly decrease cell viability compared with NC (*P < 0.05, t-test). j-l Data from MIRUMIR and miRpower showed that breast cancer patients with low expression of miR-148a, miR-148b or miR-152 had shorter survival time than those with high expression