The N-terminal polypeptide derived from vMIP-II exerts its antitumor activity in human breast cancer through CXCR4/miR-7-5p/Skp2 pathway.

Breast cancer is a malignant tumor with the highest incidence in women of the world. CXCR4 and Skp2 are highly expressed in breast cancer cells and CXCR4 was positively correlated with Skp2 by interference or overexpression. The microRNA array was used to detect the differentially expressed spectrum of micro RNAs in breast cancer cells the changes of miR-7-5p after CXCR4 inhibitor (NT21MP) treatment to block the CXCR4/SDF-1 pathway was founded. MiR-7-5p has been found to be correlated with Skp2 in various tumors in the literature, and Skp2 expression can be regulated by transfection with miR-7-5p mimics or inhibitors. The expression level of miR-7-5p was upregulated or downregulated after CXCR4 interference or overexpression. Combined with the correlation between CXCR4 and miR-7-5p in the chip results, CXCR4 may regulate Skp2 through miR-7-5p. Epithelial cells have the morphological characteristics of mesenchymal cells for some reason called epithelial-mesenchymal transformation (EMT). Transfection of miR-7-5p mimics into drug-resistant cells reduced Skp2 levels, decreased the expression of Vimentin, Snail, and slug, and increased the expression of E-cadherin. CXCR4 inhibitor (NT21MP) can reverse the EMT changes caused by miR-7-5p inhibitor. Similarly, in vivo results suggesting that CXCR4 inhibitors can reverse the EMT phenotype of drug-resistant breast cancer cells through the CXCR4/miR-7-5p/Skp2 pathway. In summary, the CXCR4/miR-7-5p/Skp2 signaling pathway plays an important role in the progression of breast cancer. This study provides a theoretical basis for the treatment of breast cancer by targeting the CXCR4 pathway.