Downregulation of RIPK4 Expression Inhibits Epithelial-Mesenchymal Transition in Ovarian Cancer through IL-6.
Downregulation of RIPK4 Expression Inhibits Epithelial-Mesenchymal Transition in Ovarian Cancer through IL-6.
复制标题
RIPK4 表达下调通过 IL-6 抑制卵巢癌的上皮间质转化。
DOI：
10.1155/2021/8875450
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发表时间：
2021
影响因子：
4.1
通讯作者：
Zhang R
中科院分区：
文献类型：
--
作者：
Yi H;Su YZ;Lin R;Zheng XQ;Pan D;Lin DM;Gao X;Zhang R
RIPK4与多种癌症类型有关，但其在卵巢癌(OC)中的作用尚不清楚。基因表达谱交互分析、RT-PCR和免疫组织化学分析结果表明，RIPK4在卵巢癌组织和细胞中的表达水平高于正常卵巢组织和细胞。在OC中，RIPK4高表达与低RIPK4表达水平相比，其总体生存率显著降低(危险率1.5(1.45~1.87)；P=0.001)。在功能实验中，RIPK4下调显著抑制OC细胞的转移行为。随后，基于TCGA数据库中593例OC患者的数据，基因集浓缩分析表明RIPK4参与了OC的上皮-间充质转化(EMT)。在分子水平上，沉默RIPK4显著下调Vimentin、N-cadherin和Twist的表达，诱导E-cadherin蛋白水平升高，抑制IL-6和STAT3水平。此外，在RIPK4沉默的OC细胞中，IL-6水平显著降低(P<；0.05)。在OC细胞中加入IL-6可拮抗RIPK4基因敲除对EMT的抑制作用。因此，我们的数据表明，下调RIPK4的表达可以通过抑制IL-6来抑制OC的EMT。这一发现可能为改善OC患者的不良预后提供新的诊断和治疗靶点。
RIPK4 has been implicated in multiple cancer types, but its role in ovarian cancer (OC) has not been clearly elucidated. Our data from Gene Expression Profiling Interactive Analysis, RT-PCR, and immunohistochemical analysis showed that RIPK4 was expressed at higher levels in OC tissues and cells than in normal ovarian tissues and cells. Increased RIPK4 expression in OC markedly correlated with a worse overall survival than lower RIPK4 expression levels (hazard rate (HR) 1.5 (1.45–1.87); P = 0.001). In functional experiments, RIPK4 downregulation significantly inhibited metastatic behaviours in OC cells. Subsequently, based on data from 593 OC patients in the TCGA database, gene set enrichment analysis revealed that RIPK4 was involved in epithelial-mesenchymal transition (EMT) in OC. At the molecular level, silencing RIPK4 significantly downregulated vimentin, N-cadherin, and Twist expression but induced an increase in the protein level of E-cadherin and inhibited the IL-6 and STAT3 levels. Moreover, IL-6 levels were significantly decreased in RIPK4-silenced OC cells (P < 0.05). The addition of IL-6 to OC cells rescued the suppressive effect of RIPK4 knockdown on EMT. Thus, our data illustrate that downregulation of RIPK4 expression can restrain EMT in OC by inhibiting IL-6. This finding may provide a novel diagnostic and therapeutic target for improving the poor prognoses of OC patients.
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