miR-23a inhibits E-cadherin expression and is regulated by AP-1 and NFAT4 complex during Fas-induced EMT in gastrointestinal cancer.
miR-23a inhibits E-cadherin expression and is regulated by AP-1 and NFAT4 complex during Fas-induced EMT in gastrointestinal cancer.
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miR-23a 抑制 E-钙粘蛋白表达，并在 Fas 诱导的胃肠道癌症 EMT 过程中受到 AP-1 和 NFAT4 复合物的调节。
DOI：
10.1093/carcin/bgt274
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发表时间：
2014
期刊：
影响因子：
4.7
通讯作者：
Zheng H, Li W, Wang Y, Xie T, Cai Y, Wang Z, Jiang B.
中科院分区：
文献类型：
--
作者：
Zheng H, Li W, Wang Y, Xie T, Cai Y, Wang Z, Jiang B.
Fas 信号传导已被证明可诱导上皮间质转化 (EMT)，从而促进胃肠道 (GI) 癌症转移，但 microRNA 在此机制中的参与仍不清楚。我们发现Fas配体（FasL）治疗抑制E-钙粘蛋白表达并通过上调miR-23a促进细胞侵袭，但miR-23a抑制剂的过度表达可以部分阻断这种活性。 FasL 诱导的细胞外信号调节激酶/丝裂原激活蛋白激酶信号传导激活激活蛋白 1 (AP-1) 复合物并抑制糖原合成酶激酶 3β 活性，从而导致 AP-1 和活化 T 细胞核因子 (NFAT4) 的核转位。 AP-1 和 NFAT4 的核积累和相互作用以及随后与 miR-23a 启动子的结合导致 miR-23a 表达增加。通过下调 Fas 受体抑制 Fas 信号传导，导致体内和体外 miR-23a 表达和细胞侵袭能力下降，以及 E-钙粘蛋白增加。对人类胃肠道癌前病变和癌症标本的评估表明，在胃肠道癌症进展过程中，FasL 和 miR-23a 的表达增加，而 E-cadherin 的表达减少。注意到这三个分子中的任何两个之间存在显着相关性。 EMT 表型被证明与晚期癌症分期和较差的预后相关。综上所述，我们的结果表明 miR-23a 参与 FasL 诱导的 EMT 过程的机制，并可能作为癌症转移的潜在治疗靶点。
Fas signaling has been shown to induce the epithelial-mesenchymal transition (EMT) to promote gastrointestinal (GI) cancer metastasis, but the involvement of microRNA in this mechanism remains unknown. We found that Fas ligand (FasL) treatment inhibited E-cadherin expression and promoted cell invasion by upregulation of miR-23a, but overexpression of the miR-23a inhibitor could partially block this activity. FasL-induced extracellular signal-regulated kinase/mitogen-activated protein kinase signaling activated the activator protein 1 (AP-1) complex and repressed glycogen synthase kinase-3β activity, which contributed to nuclear translocation of AP-1 and nuclear factor of activated T cells (NFAT4). Nuclear accumulation and interaction of AP-1 and NFAT4 and subsequent binding to the miR-23a promoter led to increased miR-23a expression. Inhibition of Fas signaling by downregulation of the Fas receptor led to a decrease in miR-23a expression and cell invasion ability in vivo and in vitro, as well as an increase in E-cadherin. Evaluation of human GI precancerous and cancer specimens showed that the expression of FasL and miR-23a increased, whereas the expression of E-cadherin decreased during GI cancer progression. A significant correlation was noted between any two of these three molecules. An EMT phenotype was shown to correlate with an advanced cancer stage and worse prognosis. Taken together, our results show that miR-23a participates in the mechanism of the FasL-induced EMT process and may serve as a potential therapeutic target for cancer metastasis.
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影响因子：
64.8
作者：
通讯作者：
--
影响因子：
37.3
作者：
Chhabra R;Dubey R;Saini N
通讯作者：
Saini N
miR-23a-27a-24-2簇的上调诱导人类胚胎肾细胞中的caspase依赖性和非依赖性凋亡。
影响因子：
3.7
作者：
Chhabra R;Adlakha YK;Hariharan M;Scaria V;Saini N
通讯作者：
Saini N
影响因子：
2.7
作者：
Hedgepeth, CM;Conrad, LJ;Klein, PS
通讯作者：
Klein, PS
影响因子：
6.4
作者：
Huang, Shenglin;He, Xianghuo;Gu, Jianren
通讯作者：
Gu, Jianren