Mir526b and Mir655 Promote Tumour Associated Angiogenesis and Lymphangiogenesis in Breast Cancer

摘要: MicroRNAs (miRNAs) are small endogenously produced RNAs, which regulate growth and development, oncogenic miRNA tumor metastasis. Tumour-associated angiogenesis lymphangiogenesis processes involving the release of factors from tumour cells into microenvioronemnt to communicate with endothelial induce vascular propagation. Here, we examined roles cyclo-oxygenase (COX)-2 induced miR526b miR655 in tumour-associated lymphangiogenesis. Ectopic overexpression poorly metastatic estrogen receptor (ER) positive MCF7 breast cancer resulted upregulation markers factor A (VEGFA); VEGFC; VEGFD; COX-2; lymphatic vessel hyaluronan receptor-1 (LYVE1); receptors VEGFR1, VEGFR2, EP4. Further, miRNA-high cell free conditioned media promoted migration tube formation by human umbilical vein (HUVECs), upregulated EP4 expression, showing paracrine stimulation microenvironment. The miRNA-induced phenotypes were abrogated antagonist or PI3K/Akt inhibitor treatments, confirming involvement pathway. Tumour supressor gene PTEN was found be downregulated high cells, that it is a target both miRNAs. inhibits hypoxia-inducible factor-1 (HIF1α) pathway, loss regulation these pathways through results VEGF expression. Moreover, tumors, marker VEGFA VEGFD expression significantly higher compared non-adjacent control, positively correlated VEGFA, VEGFC, VEGFD, CD31, LYVE1 samples. These findings further strengthen role miRNAs as biomarkers potential therapeutic abrogate cancer.