MiR-378 inhibitor- and miR-1827 mimic-treated A549-I7 cells had reduced number of metastases throughout the body of the zebrafish embryos. (A) Tumor burden per zebrafish embryo of four treatment groups, calculated by multiplying the number of cell clusters and the mean area of the cell clusters present in the embryo. (B) Number of embryos bearing successfully migrated tumor cells, expressed in percentage, was significantly lower in the miR-378 inhibitor- and miR-1827 mimic-treated groups than the scrambled inhibitor- and scrambled mimic-treated groups. (C) Metastasis was defined when there were ≥ 5 cells outside the yolk sac region. Average number of metastases was significantly higher in the scrambled inhibitor- and scrambled mimic-treated groups. (D) Bar charts detailing the percentage of embryos bearing a particular number of metastases. (E) Confocal imaging showing dispersion of treated A549-I7 cells (red) throughout the fish body. MiR-378 inhibitor- and miR-1827 mimic-treated cells were mostly confined in the yolk sac while scrambled inhibitor- and scrambled mimic-treated cells can be seen to have spread to the tail. (F) Migration was quantified by calculating the average distance between each cluster of tumor cells and site of injection (SOI). NMiR-378 inhibitor-treated = 15; NScr inhibitor-treated = 15; NMiR-1827 mimic-treated = 7; NScr mimic-treated = 19

MiR-378 inhibitor- and miR-1827 mimic-treated A549-I7 cells mitigated tumor angiogenesis in embryonic zebrafish. (A) Representative images of the zebrafish embryos subjected to whole-mount ALP staining. Arrows in black depict the ectopic vessel(s) induced by tumor cells implanted. (B) Quantification of number of ectopic vessels originating from the developing SIV in each embryo of four treatment groups. Scrambled inhibitor- and scrambled mimic-treated cells induced robust neovascular response, whereas miR-378 inhibitor- and miR-1827 mimic-treated cells were less angiogenic. (C) Quantification of length of ectopic vessels originating from the developing SIV in each embryo of four treatment groups. NMiR-378 inhibitor-treated = 44; NScr inhibitor-treated = 30; NMiR-1827 mimic-treated = 30; NScr mimic-treated = 34

Acknowledgments
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