The antimicrobial peptide Merecidin Inhibit the metastasis of triple-negative breast cancer by obstructing EMT via miR-30d-5p/vimentin

Abstract

LL-37 is an important innate immune effector molecule with great potential in antitumor therapy. Merecidin retains the most active active fragment in LL-37 with antitumor biological activity and stability. This study mainly explores the inhibitory effect of antimicrobial peptide Merecidin on triple-negative breast cancer (TNBC) cells and the mechanism of inhibiting the epithelial-mesenchymal transition (EMT) by regulating miR-30d-5p/vimentin, thereby inhibiting breast cancer metastasis. The results showed that the Merecidin was able to inhibit the proliferation, migration and invasion capacity and EMT of TNBC cells (MDA-MB-231 and MDA-MB-468) in vitro. Laser confocal localization showed that Merecidin was mainly localized in the cytoplasm of TNBC cells, and the RT-qPCR results showed that miR-30d-5p was poorly expressed in TNBC cells, and Merecidin could significantly upregulate the expression of miR-30d-5p. In addition, the Dual-luciferase reporter and q-PCR results confirmed that miR-30d-5p binds to vimentin and negatively regulates vimentin. At the same time, pull down experiments showed that Merecidin can bind to vimentin in vitro. In addition, scratch experiments and Transwell experiments showed that miR-30d-5p inhibited the migration and invasion ability of TNBC cells, while vimentin promoted the migration and invasion ability of TNBC cells. Finally, down-regulation of miR-30d-5p or overexpression of vimentin could partially counteract the inhibitory effect of Merecidin on TNBC cell migration, invasion ability and EMT. In the nude mouse MDA-MB-231 subcutaneous tumor model, Merecidin significantly inhibited tumor growth and cell proliferation and upregulated the expression of miR-30d-5p in tumor tissues, inhibiting the expression of vimentin and EMT. In conclusion, Merecidin can effectively inhibit the proliferation, migration and invasion ability of TNBC cancer cells; localization in the cytoplasm; By regulating miR-30d-5p/vimentin, it can effectively hinder the EMT process, thereby effectively inhibiting the migration and invasion of TNBC cells. These findings provide new insights into the molecular function of Merecidin, suggesting its potential as a therapeutic agent for TNBC.