Sinomenine Inhibits Vasculogenic Mimicry and Migration of Breast Cancer Side Population Cells via Regulating miR-340-5p/SIAH2 Axis

Hypoxia and its induced vasculogenic mimicry (VM) formation, which both closely related with stem-like side population (SP) cells, are the main culprits leading to tumor invasion and metastasis. Sinomenine exhibits excellent anticancer activity in breast cancer, but whether and how it affects hypoxia-triggered VM formation in breast cancer SP cells remains unclear. In this study, breast cancer SP cells were sorted from MDA-MB-231 cells and cultured with sinomenine under hypoxic conditions. Sinomenine obviously repressed the migration and VM formation of breast cancer SP cells. Through downregulating SIAH2 and HIF-1α, sinomenine can inhibit epithelial-mesenchymal transition process of breast cancer SP cells. SIAH2 was identified as a target of miR-340-5p and was downregulated by it, and sinomenine can upregulate miR-340-5p. Hypoxia-induced downregulation of miR-340-5p and activation of SIAH2/HIF-1α pathway can be both counteracted by the sinomenine. Moreover, miR-340-5p inhibition and SIAH2 overexpression can partly counteract the anticancer effects of sinomenine. Taken together, sinomenine inhibits hypoxia-caused VM formation and metastasis of breast cancer SP cells by regulating the miR-340-5p/SIAH2 axis.