Delivery of inhibitor of growth 4 (ING4) gene significantly inhibits proliferation and invasion and promotes apoptosis of human osteosarcoma cells.
Delivery of inhibitor of growth 4 (ING4) gene significantly inhibits proliferation and invasion and promotes apoptosis of human osteosarcoma cells.
复制标题
生长抑制剂4（ING4）基因的递送显着抑制人骨肉瘤细胞的增殖和侵袭并促进细胞凋亡。
DOI：
10.1038/srep07380
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发表时间：
2014-12-09
影响因子：
4.6
通讯作者：
Mao C
中科院分区：
文献类型：
--
作者：
Li M;Zhu Y;Zhang H;Li L;He P;Xia H;Zhang Y;Mao C
越来越多的证据表明，生长抑制因子4（inhibitor of growth 4，ING 4）是ING家族蛋白的新成员，通过多种途径在不同肿瘤的发生发展中发挥重要作用。然而，ING 4在人骨肉瘤中的功能仍不清楚。为了解ING 4对骨肉瘤的抑制作用及其机制，我们构建了真核表达载体pEGFP-ING 4，并将其转染人骨肉瘤细胞。研究转染细胞中ING 4过表达对骨肉瘤细胞增殖、凋亡和侵袭能力的影响。通过稳定转染pEGFP-ING 4基因，ING 4在骨肉瘤细胞中的表达上调，使细胞周期发生S期缩短和G 0/G1期阻滞，抑制细胞增殖;通过激活线粒体途径诱导细胞凋亡;通过下调基质金属蛋白酶2（MMP-2）和MMP-9的表达，抑制细胞侵袭。此外，ING 4水平升高可阻断NF-κB信号通路，下调其靶蛋白的表达。我们的研究结果表明，ING 4可以通过线粒体信号通路和NF-κB信号通路抑制骨肉瘤的进展，ING 4基因治疗是一种有希望的治疗骨肉瘤的方法。
Growing evidence has suggested that inhibitor of growth 4 (ING4), a novel member of ING family proteins, plays a critical role in the development and progression of different tumors via multiple pathways. However, the function of ING4 in human osteosarcoma remains unclear. To understand its potential roles and mechanisms in inhibiting osteosarcoma, we constructed an expression vector pEGFP-ING4 and transfected the human osteosarcoma cells using this vector. We then studied the effects of over-expressed ING4 in the transfected cells on the proliferation, apoptosis and invasion of the osteosarcoma cells. The up-regulation of ING4 in the osteosarcoma cells, arising from the stable pEGFP-ING4 gene transfection, was found to significantly inhibit the cell proliferation by the cell cycle alteration with S phase reduction and G0/G1 phase arrest, induce cell apoptosis via the activation of the mitochondria pathway, and suppress cell invasion through the down-regulation of the matrix metalloproteinase 2 (MMP-2) and MMP-9 expression. In addition, increased ING4 level evoked the blockade of NF-κB signaling pathway and down-regulation of its target proteins. Our work suggests that ING4 can suppress osteosarcoma progression through signaling pathways such as mitochondria pathway and NF-κB signaling pathway and ING4 gene therapy is a promising approach to treating osteosarcoma.
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影响因子：
2.8
作者：
Li, Shijie;Fan, Tianli;Ren, Xuequn
通讯作者：
Ren, Xuequn
影响因子：
21.3
作者：
Kawauchi, Keiko;Araki, Keigo;Tanaka, Nobuyuki
通讯作者：
Tanaka, Nobuyuki
影响因子：
64.8
作者：
Garkavtsev, I;Kozin, SV;Jain, RK
通讯作者：
Jain, RK
影响因子：
56.9
作者：
HUANG, HJS;YEE, JK;LEE, WH
通讯作者：
LEE, WH
影响因子：
--
作者：
Gaspar N;Di Giannatale A;Geoerger B;Redini F;Corradini N;Enz-Werle N;Tirode F;Marec-Berard P;Gentet JC;Laurence V;Piperno-Neumann S;Oberlin O;Brugieres L
通讯作者：
Brugieres L