MiR-145 directly targets p70S6K1 in cancer cells to inhibit tumor growth and angiogenesis.
MiR-145 directly targets p70S6K1 in cancer cells to inhibit tumor growth and angiogenesis.
复制标题
MiR-145 直接靶向癌细胞中的 p70S6K1，抑制肿瘤生长和血管生成
DOI：
10.1093/nar/gkr730
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发表时间：
2012-01
影响因子：
14.9
通讯作者：
Jiang BH
中科院分区：
文献类型：
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作者：
Xu Q;Liu LZ;Qian X;Chen Q;Jiang Y;Li D;Lai L;Jiang BH
miR-145可以调节细胞凋亡、增殖、神经发育和干细胞分化。先前的研究表明，miR-145在人结肠癌细胞中下调。然而，miR-145用于调控结肠癌发生和血管生成的分子机制仍有待阐明。在这里，我们发现miR-145的表达在结肠癌和卵巢癌组织和细胞系中下调。miR-145通过与p70 S6 K1的3′-UTR结合抑制其转录后表达。p70 S6 K1的下游分子血管生成因子缺氧诱导因子1（HIF-1）和血管内皮生长因子（VEGF）通过miR-145过表达而降低。P70 S6 K1拯救miR-145抑制的HIF-1和VEGF水平、肿瘤发生和肿瘤血管生成。此外，miR-145水平与结肠癌组织中p70 S6 K1蛋白的量呈负相关。总之，这些研究表明，miR-145作为肿瘤抑制因子，通过靶向p70 S6 K1下调HIF-1和VEGF表达，从而抑制肿瘤生长和血管生成。miR-145的拯救可能是未来结肠癌治疗应用的基本原理。
MiR-145 can regulate cell apoptosis, proliferation, neural development and stem cell differentiation. Previous studies indicate that miR-145 is downregulated in human colon cancer cells. However, the molecular mechanisms of miR-145 used to regulate colon carcinogenesis and angiogenesis remain to be clarified. Here, we show that the expression of miR-145 is downregulated in colon and ovarian cancer tissues and cell lines. MiR-145 inhibits p70S6K1 post-transcriptional expression by binding to its 3′-UTR. The angiogenic factors hypoxia-inducible factor 1 (HIF-1) and vascular endothelial growth factor (VEGF), which are downstream molecules of p70S6K1, are decreased by miR-145 overexpression. P70S6K1 rescues miR-145-suppressed HIF-1 and VEGF levels, tumorigenesis and tumor angiogenesis. Furthermore, the miR-145 level is inversely correlated with the amount of p70S6K1 protein in colon cancer tissues. Taken together, these studies suggest that miR-145 serves as a tumor suppressor which downregulates HIF-1 and VEGF expression by targeting p70S6K1, leading to the inhibition of tumor growth and angiogenesis. The miR-145 rescue could be a rationale for therapeutic applications in colon cancer in the future.
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影响因子：
64.8
作者：
Cordes KR;Sheehy NT;White MP;Berry EC;Morton SU;Muth AN;Lee TH;Miano JM;Ivey KN;Srivastava D
通讯作者：
Srivastava D
影响因子：
4.1
作者：
Cho, William C. S.;Chow, Andrew S. C.;Au, Joseph S. K.
通讯作者：
Au, Joseph S. K.
影响因子：
12.3
作者：
Larsson E;Fredlund Fuchs P;Heldin J;Barkefors I;Bondjers C;Genové G;Arrondel C;Gerwins P;Kurschat C;Schermer B;Benzing T;Harvey SJ;Kreuger J;Lindahl P
通讯作者：
Lindahl P
影响因子：
3.7
作者：
Gregersen LH;Jacobsen AB;Frankel LB;Wen J;Krogh A;Lund AH
通讯作者：
Lund AH
影响因子：
8.8
作者：
通讯作者：
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