FIGURE 4.

Upregulation of miR-3965 and miR-3470a with corresponding target suppression in 27-day PC3MLuc2a-EV treated mouse bones. miR-3965 and miR3470a (analogous to human miR21-5p and miR1285-5p) were found to have an increased expression in 27-day PC3MLuc2a-EV treated mouse bones. Target genes of both microRNAs were found to be simultaneously downregulated in the same EV-treated mouse bones (A) targets of miR-3965 (B) targets of miR3470a. (C) Gene targets which are the same in both mice and humans (STAG2, SLC35E3, NDNF, ZCCHC4, METTL21A, ZFX, ZBTB25, COX7B, and CLIP3) for these two miRNAs were examined in vitro treatment via the treatment of human osteoblasts (hOBs) with EVs isolated from PC3MLuc2a cells compared to EVs from control PNT1A cells. All results were repeated in triplicate and significant at p < 0.0001, except for SLC35EB p = 0.016 as determined by Wald test for significance.