Ribosomal L22-like1 (RPL22L1) Promotes Ovarian Cancer Metastasis by Inducing Epithelial-to-Mesenchymal Transition.
Ribosomal L22-like1 (RPL22L1) Promotes Ovarian Cancer Metastasis by Inducing Epithelial-to-Mesenchymal Transition.
复制标题
核糖体 L22-like1 (RPL22L1) 通过诱导上皮间质转化促进卵巢癌转移
DOI：
10.1371/journal.pone.0143659
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Jin Y
中科院分区：
文献类型：
--
作者：
Wu N;Wei J;Wang Y;Yan J;Qin Y;Tong D;Pang B;Sun D;Sun H;Yu Y;Sun W;Meng X;Zhang C;Bai J;Chen F;Geng J;Lee KY;Fu S;Jin Y
双微小染色体（DM）对癌症进展具有重要意义，因为癌基因经常在其上扩增。我们以前检测到一个功能不确定的基因扩增DM，核糖体L22样1（RPL 22 L1）。RPL 22 L1与癌症进展之间的关系尚不清楚。在这里，RPL 22 L1的特征在于其在卵巢癌（OC）转移中的作用，并检查了其潜在机制。使用从癌症基因组图谱和基因表达综合数据库获得的数据分析OC细胞中RPL 22 L1的DNA拷贝数和mRNA表达。对临床OC标本进行免疫组化分析，并评估其表达水平与临床病理因素之间的关系。此外，进行体内和体外测定以了解RPL 22 L1在OC中的作用。RPL 22 L1在OC组织中的表达高于正常组织，其表达水平与浸润和淋巴结转移高度正相关（P <0. 05）。RPL 22 L1过表达显著增强裸鼠腹腔内异种移植瘤的发展，并促进体外侵袭和迁移。RPL 22 L1基因敲低可显著抑制UACC-1598细胞的侵袭和迁移。此外，RPL 22 L1过表达上调间充质标志物波形蛋白、纤连蛋白和α-SMA，降低上皮标志物E-钙粘蛋白、α-连环蛋白和β-连环蛋白的表达。RPL 22 L1抑制降低波形蛋白和N-钙粘蛋白的表达。这些结果表明RPL 22 L1诱导上皮向间充质转化（EMT）。我们的数据表明，DMs扩增的基因RPL 22 L1在维持OC的侵袭性表型和通过诱导EMT触发细胞转移中是至关重要的。它可以作为一种新的预后指标和/或有效的治疗OC的目标。
Double minute chromosomes (DMs) have important implications for cancer progression because oncogenes frequently amplified on them. We previously detected a functionally undefined gene amplified on DMs, Ribosomal L22-like1 (RPL22L1). The relationship between RPL22L1 and cancer progression is unknown. Here, RPL22L1 was characterized for its role in ovarian cancer (OC) metastasis and its underlying mechanism was examined. DNA copy number and mRNA expression of RPL22L1 in OC cells was analyzed using data obtained from The Cancer Genome Atlas and the Gene Expression Omnibus database. An immunohistochemical analysis of clinical OC specimens was performed and the relationships between expression level and clinicopathological factors were evaluated. Additionally, in vivo and in vitro assays were performed to understand the role of RPL22L1 in OC. RPL22L1 expression was higher in OC specimens than in normal tissues, and its expression level was highly positively correlated with invasion and lymph node metastasis (P < 0.05). RPL22L1 over-expression significantly enhanced intraperitoneal xenograft tumor development in nude mice and promoted invasion and migration in vitro. Additionally, RPL22L1 knockdown remarkably inhibited UACC-1598 cells invasion and migration. Further, RPL22L1 over-expression up-regulated the mesenchymal markers vimentin, fibronectin, and α-SMA, reduced expression of the epithelial markers E-cadherin, α-catenin, and β-catenin. RPL22L1 inhibition reduced expression of vimentin and N-cadherin. These results suggest that RPL22L1 induces epithelial-to-mesenchymal transition (EMT). Our data showed that the DMs amplified gene RPL22L1 is critical in maintaining the aggressive phenotype of OC and in triggering cell metastasis by inducing EMT. It could be employed as a novel prognostic marker and/or effective therapeutic target for OC.