The synergistic regulation of VEGF-mediated angiogenesis through miR-190 and target genes

Abstract

VEGF is a major contributor to angiogenesis, a vital process in normal growth and development and tumor transition. However, the current clinical efficacy of VEGF inhibitors is limited, and the molecular mechanism underlying VEGF regulation remains to be elucidated. Here we show that miR-190 directly targets a group of angiogenic effectors besides VEGF per se. Noted, these effectors can transcriptionally regulate VEGF expression in an intracellular or intercellular manner, thus demonstrating that miR-190 modulates the VEGF-mediated tumor angiogenesis at three levels. The synergistic effect of miR-190 and its target genes demonstrates a complex but apparently more stable system, allowing for the tight control of the level of VEGF. Finally, we showed that miR-190 significantly suppresses tumor metastasis, especially angiogenesis. Together, these results indicate that miR-190 is a promising antitumor target in clinical applications.

Identification of Viscum album L. miRNAs and prediction of their medicinal values

“…It is generally accepted that VEGF is a major driver of the angiogenic process in physiological and pathological processes. VEGF and its receptors are often found overexpressed in tumors [ 55 , 56 ]. Suppression of the essential molecules in VEGF signaling pathway, such as phospholipase C gamma 1 (PLCG1) possibly targeted by val-miR615 and val-miR1086, tyrosine-protein kinase Src possibly targeted by val-miR834 and val-miR1086, may block the angiogenic activity of tumor tissue, resulting in tumor vascular regression and anti-tumor effects.…”

Dysregulation of microRNAs in triple-negative breast cancer

“…Hao et al (2014) brought attention to the role of miR-190a in suppression of tumor metastasis via interaction with VEGF-mediated tumor angiogenesis [28]. In breast cancer, overexpression of miR-190a has inhibited the cell migration and invasiveness.…”

MiR-190b, the highest up-regulated miRNA in ERα-positive compared to ERα-negative breast tumors, a new biomarker in breast cancers?

“…MicroRNA expression profile associated with response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer patients included miR-190b [ 40 ]. However none of these studies explored mechanism of action of miR-190b and its targets did not have been well described contrary to miR-190 that could interfere with VEGF-mediated angiogenesis [ 41 ]. Morevover miR-190b has not been selected by previous microarray breast cancer studies [ 16 , 17 , 19 , 42 ] so we tried to decipher its properties in breast cancer.…”