circDCUN1D4 suppresses tumor metastasis and glycolysis in lung adenocarcinoma by stabilizing TXNIP expression.
circDCUN1D4 suppresses tumor metastasis and glycolysis in lung adenocarcinoma by stabilizing TXNIP expression.
复制标题
DOI：
10.1016/j.omtn.2020.11.012
复制
发表时间：
2021-03-05
期刊：
影响因子：
--
通讯作者：
Jiang F
中科院分区：
文献类型：
--
作者：
Liang Y;Wang H;Chen B;Mao Q;Xia W;Zhang T;Song X;Zhang Z;Xu L;Dong G;Jiang F
环状RNA（circRNA）的异常表达通过与RNA结合蛋白（RBP）的相互作用参与癌症进展。在本文中，我们在circBase中筛选A549细胞的circRNA表达和人抗原R（HuR）的交联免疫沉淀（CLIP）数据，HuR是一种广泛研究的RBP，并鉴定了一种circRNA，circ缺陷的cullin neddylation 1结构域包含4（circDCUN 1D 4），来源于DCUN 1D 4基因转录物。circDCUN 1D 4在DExH盒解旋酶9（DHX 9）的介导下在肿瘤样品中下调，DHX 9通过结合侧翼序列中的反向重复Alus（IRAlus）抑制circRNA的形成。circDCUN 1D 4缺失促进体外侵袭和体内转移。重要的是，circDCUN 1D 4和HuR之间的相互作用增加了HuR向细胞质的运输。circDCUN 1D 4作为一个支架，促进HuR蛋白和硫氧还蛋白相互作用蛋白（TXNIP）mRNA之间的相互作用，这增强了TXNIP mRNA的稳定性。此外，circDCUN 1D 4通过碱基互补直接与TXNIP mRNA相互作用，表明形成了circDCUN 1D 4/HuR/TXNIP RNA-蛋白质三元复合物。此外，circDCUN 1D 4以TXNIP依赖性方式抑制肺癌细胞的转移和糖酵解。临床上，circDCUN 1D 4的下调表达在淋巴结转移组织中更普遍，并且作为肺腺癌（LUAD）患者总生存的独立危险因素。这些发现表明，一种新的circRNA，circDCUN 1D 4，参与LUAD的转移和糖酵解。Liang等人等报道，环状RNA，circDCUN 1D 4，可以通过与HuR相互作用并增加HuR细胞质保留以维持TXNIP mRNA的稳定性，从而抑制转移和糖酵解，在肺腺癌中起肿瘤抑制剂的作用。
Aberrant expression of circular RNAs (circRNAs) is involved in cancer progression through interaction with RNA-binding proteins (RBPs). Herein, we screened circRNA expression of A549 cells in circBase and the crosslinking immunoprecipitation (CLIP) data of human antigen R (HuR), an extensively studied RBP, and identified a circRNA, circ-defective in cullin neddylation 1 domain containing 4 (circDCUN1D4), originating from the DCUN1D4 gene transcript. circDCUN1D4 is downregulated in tumor samples under the mediation of DExH-box helicase 9 (DHX9), which inhibits the formation of circRNA by binding inverted repeat Alus (IRAlus) in flanking sequences. circDCUN1D4 depletion promoted invasion in vitro and metastasis in vivo. Importantly, the interaction between circDCUN1D4 and HuR increased the transportation of HuR to the cytoplasm. circDCUN1D4 acts as a scaffold to facilitate the interaction between the HuR protein and thioredoxin-interacting protein (TXNIP) mRNA, which enhances the stability of the TXNIP mRNA. Additionally, circDCUN1D4 directly interacts with TXNIP mRNA through base complementation, indicating the formation of the circDCUN1D4/HuR/TXNIP RNA-protein ternary complex. Furthermore, circDCUN1D4 suppressed metastasis and glycolysis of lung cancer cells in a TXNIP-dependent manner. Clinically, the downregulated expression of circDCUN1D4 was more prevalent in lymph node metastatic tissues and served as an independent risk factor for the overall survival of lung adenocarcinoma (LUAD) patients. These findings demonstrated that a novel circRNA, circDCUN1D4, is involved in the metastasis and glycolysis of LUAD. Liang et al. reported that circular RNA, circDCUN1D4, could act as the tumor suppressor in lung adenocarcinoma by interacting with HuR and increasing HuR cytoplasmic retention to maintain the stability of TXNIP mRNA, which suppressed metastasis and glycolysis.
登录
查看更多内容
DOI：
10.1038/nrc.2017.99
发表时间：
2018-01
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
Anastasiadou E;Jacob LS;Slack FJ
通讯作者：
Slack FJ
影响因子：
5.3
作者：
Lafarga, Vanesa;Cuadrado, Ana;Nebreda, Angel R.
通讯作者：
Nebreda, Angel R.
影响因子：
64.8
作者：
Aktas, Tugce;Ilik, Ibrahim Avsar;Akhtar, Asifa
通讯作者：
Akhtar, Asifa
circTP63 作为 ceRNA 通过上调 FOXM1 促进肺鳞状细胞癌进展
影响因子：
16.6
作者：
Cheng, Zhuoan;Yu, Chengtao;Qin, Wenxin
通讯作者：
Qin, Wenxin
影响因子：
3.2
作者：
Alhawiti NM;Al Mahri S;Aziz MA;Malik SS;Mohammad S
通讯作者：
Mohammad S