骨髓來源內(nèi)皮祖細(xì)胞（EPCs）有助于小鼠和人腫瘤組織內(nèi)血管生成現(xiàn)象依賴性生長。內(nèi)皮祖細(xì)胞通過旁分泌促血管生成因子以及促進(jìn)管腔直接進(jìn)入發(fā)芽狀態(tài)的新生血管來調(diào)節(jié)血管生成開關(guān)。
微小RNA（miRNA）是參與多種細(xì)胞生物學(xué)過程的關(guān)鍵調(diào)節(jié)因子包括血管生成,。然而,， miRNA 是否對骨髓來源內(nèi)皮祖細(xì)胞介導(dǎo)的血管生成有作用仍然不明,。
近日,，一項(xiàng)最新研究表明遺傳消融微小RNA加工Dicer酶后，導(dǎo)致循環(huán)內(nèi)皮祖細(xì)胞數(shù)量下降,，引發(fā)血管生成抑制,，腫瘤生長受損。
此外,，微小RNA的全基因組深度測序揭示其中miR-10b和miR-196b是腫瘤EPC內(nèi)在的miRNA,，miR-10b和miR-196b先前已確定是HOX信號和成人干細(xì)胞分化的關(guān)鍵調(diào)節(jié)因子。
值得注意的是,，科研人員發(fā)現(xiàn)miR-10b和miR-196b對血管內(nèi)皮生長因子（VEGF）刺激有反應(yīng),，并且兩者在人乳腺腫瘤血管中的表達(dá)是升高的。
引人注目的是,，作用于miR-10B和miR-196b后導(dǎo)致血管生成介導(dǎo)的小鼠腫瘤生長顯著被抑制,。針對這些miRNAs可能是一種新的抑制腫瘤血管生成的策略。（生物谷：Bioon.com）
doi:10.1158/0008-5472.CAN-12-0271
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MicroRNAs regulate tumor angiogenesis modulated by endothelial progenitor cells.
Prue N Plummer1, Ruth Freeman1, Ryan Taft2, Jelena Vider1, Michael Sax1, s et al.
Bone marrow (BM)-derived endothelial progenitor cells (EPCs), contribute to the angiogenesis dependent growth of tumors in mice and humans. EPCs regulate the angiogenic switch via paracrine secretion of proangiogenic growth factors, and by direct luminal incorporation into sprouting nascent vessels. MicroRNAs (miRNAs) have emerged as key regulators of several cellular processes including angiogenesis; however, whether miRNAs contribute to BM-mediated angiogenesis has remained unknown. Here, we show that genetic ablation of microRNA processing enzyme Dicer, specifically in the BM, decreased the number of circulating EPCs, resulting in angiogenesis suppression and impaired tumor growth. Furthermore, genome-wide deep sequencing of small RNAs revealed tumor EPC-intrinsic miRNAs including miR-10b and miR-196b; which have been previously identified as key regulators of HOX signaling and adult stem cell differentiation. Notably, we found that both miR-10b and miR-196b, are responsive to vascular endothelial growth factor (VEGF) stimulation, and show elevated expression in human high-grade breast tumor vasculature. Strikingly, targeting miR-10b and miR-196b led to significant defects in angiogenesis-mediated tumor growth in mice. Targeting these miRNAs may constitute a novel strategy for inhibiting tumor angiogenesis.
