MicroRNA-645, up-regulated in human adencarcinoma of gastric esophageal junction, inhibits apoptosis by targeting tumor suppressor IFIT2.
MicroRNA-645, up-regulated in human adencarcinoma of gastric esophageal junction, inhibits apoptosis by targeting tumor suppressor IFIT2.
复制标题
DOI：
10.1186/1471-2407-14-633
复制
发表时间：
2014-08-29
期刊：
影响因子：
3.8
通讯作者：
Gao S
中科院分区：
文献类型：
--
作者：
Feng X;Wang Y;Ma Z;Yang R;Liang S;Zhang M;Song S;Li S;Liu G;Fan D;Gao S
越来越多的证据表明，miRNAs在肿瘤的发生和发展中起着重要作用，然而，miRNAs在胃食管交界处腺癌（AGEJ）发生中的作用仍不清楚。胃癌细胞株为SGC-7901和BGC-823。采用qRT-PCR检测miR-645和IFIT 2（Interferon-induced protein with tetratricopeptide repeats 2）的表达，采用Western blotting和免疫组化检测IFIT 2的表达。流式细胞仪检测细胞凋亡。进行miR-645抑制剂、模拟物和质粒-IFIT 2转染以研究功能的丧失和获得。Caspase-3/7活性测定。在本研究中，我们报道了与配对的非癌组织相比，miR-645在AGEJ临床标本中的表达增加。我们还在两种胃癌（GC）细胞系SGC 7901和BGC-823中观察到显著的miR-645上调，这两种细胞系被用作细胞模型，因为迄今为止还没有建立可用的AGEJ细胞系。我们发现，抑制miR-645可以通过上调IFIT 2（一种通过线粒体途径介导凋亡的介质，在其mRNA的3′UTR中具有miR-645的潜在结合位点）显著地使SGC 7901和BGC-823细胞对血清饥饿和化疗药物诱导的凋亡敏感。进一步的研究表明，IFIT 2在SGC 7901和BGC-823细胞以及AGEJ组织中的表达降低。IFIT 2异位表达可促进细胞凋亡，提示IFIT 2可能在AGEJ的发生发展中起抑制作用。此外，与对照组相比，miR-645的抑制诱导IFIT 2的上调和caspase-3/7活性的增加。我们的数据表明，miR-645在人AGEJ中作为癌基因发挥作用，至少部分通过靶向IFIT 2。本文的在线版本（doi：10.1186/1471-2407-14-633）包含补充材料，可供授权用户使用。
An increasing body of evidence indicates that miRNAs have a critical role in carcinogenesis and cancer progression; however, the role of miRNAs in the tumorigenesis of adencarcinoma of gastric esophageal junction (AGEJ) remains largely unclear. The SGC7901 and BGC-823 gastric cancer cell lines were used. The expressions of miR-645 and IFIT2 (Interferon-induced protein with tetratricopeptide repeats 2) were examined by qRT-PCR, The expressions of IFIT2 was examined by western blotting and immunohistochemistry assay. The cell apoptosis was determined by FACS. MiR-645 inhibitor, mimics and plasmid-IFIT2 transfections were performed to study the loss- and gain-function. Caspase-3/7 activity was examined by caspase-3/7 assay. In the present study, we have reported an increased expression of miR-645 in AGEJ clinical specimens compared with paired non-cancerous tissues. We also observed a significant miR-645 up-regulation in two gastric cancer (GC) cell lines, SGC7901 and BGC-823, which were used as cell models because there was no available AGEJ cell lines established to date. We found that inhibition of miR-645 could sensitize dramatically SGC7901 and BGC-823 cells to both serum starvation– and chemotherapeutic drug–induced apoptosis by up-regulating IFIT2, a mediator of apoptosis via a mitochondrial pathway, with a potential binding site for miR-645 in its mRNA’s 3′UTR. Further investigation exhibited that IFIT2 expression decreases in SGC7901 and BGC-823 cells and AGEJ tissues. IFIT2 ectopic expression leads to promotion of cell apoptosis, indicating that IFIT2 may function as a suppressor in the development of AGEJ. Furthermore, inhibition of miR-645 induces up-regulation of IFIT2 and increased caspase-3/7 activity compared with control groups. Our data suggest that miR-645 functions as an oncogene in human AGEJ by, at least partially through, targeting IFIT2. The online version of this article (doi:10.1186/1471-2407-14-633) contains supplementary material, which is available to authorized users.
登录
查看更多内容
影响因子：
56.9
作者：
KARUPIAH, G;XIE, QW;MACMICKING, JD
通讯作者：
MACMICKING, JD
影响因子：
10.3
作者：
Gammon, MD;Schoenberg, JB;Fraumeni, JF
通讯作者：
Fraumeni, JF
影响因子：
14.9
作者：
Griffiths-Jones S;Grocock RJ;van Dongen S;Bateman A;Enright AJ
通讯作者：
Enright AJ
影响因子：
9.7
作者：
Liu, Tao;Tang, Hua;Li, Xin
通讯作者：
Li, Xin
影响因子：
15.9
作者：
Liu, Xi;Sempere, Lorenzo F.;Dmitrovsky, Ethan
通讯作者：
Dmitrovsky, Ethan