Salvia miltiorrhiza-derived microRNA58 inhibits tumor growth by targeting Krüppel-like factor 3 in human endothelial cells

Background: The abnormal proliferation and migration of endothelial cells is closely associated with vascular growth, which regulates angiogenesis and cancer cell progression. Salvia miltiorrhiza (S. miltiorrhiza) is an important medicinal herb that exerts anti-tumor effects. The microRNAs (miRNAs) in S. miltiorrhiza play an important role in both their original system and other species. However, it has not yet been determined whether S. miltiorrhiza-derived miRNAs protect human umbilical vein endothelial cells (HUVECs) by inhibiting proliferation and migration across species. This study aims to investigate the anti-angiogenic and anti-tumor activity of S. miltiorrhiza-derived miR-58 (Sal-miR-58) in HUVECs and B16 tumor-bearing C57BL/6 mouse models, respectively. Methods: To identify S. miltiorrhiza miRNAs, high-throughput sequencing was performed, followed by Sal-miR-58 level quantification using quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). The interaction between Sal-miR-58 and the Krüppel-like factor 3 (KLF3) three prime untranslated region (3'-UTR) was validated by luciferase assay. For in vivo anti-tumor assessment, B16 tumor-bearing C57BL/6 mouse models were used. Results: Exogenously administered Sal-miR-58 was detected in mouse tissues and HUVEC cultures, demonstrating high stability under boiling and acidic conditions. It inhibited cancer development in vivo and attenuated the platelet-derived growth factor BB (PDGF-BB)-induced proliferation and migration of the HUVECs in vitro. Mechanistically, Sal-miR-58 was shown to directly bind to the KLF3 3'-UTR, downregulating its expression. Conclusions: Sal-miR-58 exerts anti-tumor effects by targeting KLF3 messenger RNA (mRNA). This targeting inhibits abnormal HUVEC proliferation and migration in vitro, thereby impeding tumor angiogenesis development.