p53-responsive miR-194 inhibits thrombospondin-1 and promotes angiogenesis in colon cancers.
p53-responsive miR-194 inhibits thrombospondin-1 and promotes angiogenesis in colon cancers.
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p53 响应性 miR-194 抑制血小板反应蛋白-1 并促进结肠癌中的血管生成。
DOI：
10.1158/0008-5472.can-11-1124
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发表时间：
2011
期刊：
影响因子：
11.2
通讯作者：
Thomas-Tikhonenko,Andrei
中科院分区：
文献类型：
--
作者：
Sundaram,Prema;Hultine,Stacy;Smith,LaurenM;Dews,Michael;Fox,JamieL;Biyashev,Dauren;Schelter,JanellM;Huang,Qihong;Cleary,MicheleA;Volpert,OlgaV;Thomas-Tikhonenko,Andrei
血栓反应蛋白-1(TSP-1)是由THBS1基因编码的内源性血管生成抑制因子，其启动子由P53激活。在晚期结直肠癌(CRC)中，尽管P53经常丢失，但其表达持续或略有增加。在这里，我们确定在HCT116 CRC细胞中，p53激活了THBS1的初级转录，但不能提高THBS1的mRNA或蛋白水平，这意味着转录后调控由microRNAs(MiRNA)进行。在Dice缺陷的HCT116变体中进行的全球miRNA功能增益筛查中，几个miRNA负调控THBS1的mRNA和蛋白水平，其中之一是miR-194。值得注意的是，与已发表的数据一致，p53上调了THBS1逆转录病毒转导的HCT116细胞中miR-194的表达，导致TSP-1水平下降。这种负面作用是由THBS1 3‘-非翻译区的单个miR-194互补位点介导的，它的消除导致TSP-1重新激活，Matrigel栓血管生成受阻，HCT116异种移植瘤生长减慢。相反，在HCT116/THBS1细胞中瞬时过表达miR-194可促进Matrigel血管生成，其在RAS诱导的小鼠结肠癌中的稳定过表达可增加微血管密度和血管大小。虽然miR-194对肿瘤生长的总体贡献取决于上下文，但在缺血期间，p53诱导的这种胃肠道特异性miRNA的激活可以促进血管生成和促进组织修复。©2011 AACR。
Thrombospondin-1 (TSP-1) is an endogenous inhibitor of angiogenesis encoded by theTHBS1gene, whose promoter is activated by p53. In advanced colorectal cancers (CRC), its expression is sustained or even slightly increased despite frequent loss of p53. Here, we determined that in HCT116 CRC cells, p53 activates the THBS1 primary transcript, but fails to boost THBS1 mRNA or protein levels, implying posttranscriptional regulation by microRNAs (miRNA). In a global miRNA gain-of-function screen done in the Dicer-deficient HCT116 variant, several miRNAs negatively regulated THBS1 mRNA and protein levels, one of them being miR-194. Notably, in agreement with published data, p53 upregulated miR-194 expression in THBS1 retrovirus-transduced HCT116 cells, leading to decreased TSP-1 levels. This negative effect was mediated by a single miR-194 complementary site in the THBS1 3′-untranslated region, and its elimination resulted in TSP-1 reactivation, impaired angiogenesis in Matrigel plugs, and reduced growth of HCT116 xenografts. Conversely, transient overexpression of miR-194 in HCT116/THBS1 cells boosted Matrigel angiogenesis, and its stable overexpression in Ras-induced murine colon carcinomas increased microvascular densities and vessel sizes. Although the overall contribution of miR-194 to neoplastic growth is context dependent, p53-induced activation of this GI tract–specific miRNA during ischemia could promote angiogenesis and facilitate tissue repair.Cancer Res; 71(24); 7490–501. ©2011 AACR.
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接受根治性前列腺切除术的病理阶段 T3 前列腺癌患者中血小板反应蛋白-1 的表达：与 p53 改变、肿瘤血管生成和肿瘤进展的相关性。
影响因子：
2.1
作者：
G. Grossfeld;P. Carroll;Neil Lindeman;M. Meng;S. Groshen;An‐Chen Feng;D. Hawes;R. Cote
通讯作者：
R. Cote
影响因子：
50.3
作者：
Pichiorri F;Suh SS;Rocci A;De Luca L;Taccioli C;Santhanam R;Zhou W;Benson DM Jr;Hofmainster C;Alder H;Garofalo M;Di Leva G;Volinia S;Lin HJ;Perrotti D;Kuehl M;Aqeilan RI;Palumbo A;Croce CM
通讯作者：
Croce CM
影响因子：
20.3
作者：
Zaslavsky, Alexander;Baek, Kwan-Hyuck;Ryeom, Sandra
通讯作者：
Ryeom, Sandra
影响因子：
3.5
作者：
Gasparini, G;Toi, M;Gion, M
通讯作者：
Gion, M
影响因子：
16
作者：
Mestdagh P;Boström AK;Impens F;Fredlund E;Van Peer G;De Antonellis P;von Stedingk K;Ghesquière B;Schulte S;Dews M;Thomas-Tikhonenko A;Schulte JH;Zollo M;Schramm A;Gevaert K;Axelson H;Speleman F;Vandesompele J
通讯作者：
Vandesompele J