Long noncoding RNA TP53TG1 promotes pancreatic ductal adenocarcinoma development by acting as a molecular sponge of microRNA-96
Long noncoding RNA TP53TG1 promotes pancreatic ductal adenocarcinoma development by acting as a molecular sponge of microRNA-96
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长非编码RNA TP53TG1通过充当microRNA-96的分子海绵促进胰腺导管腺癌的发展
DOI：
10.1111/cas.14136
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发表时间：
2019-08-07
期刊：
影响因子：
5.7
通讯作者：
Zhang, Xianghong
中科院分区：
文献类型：
--
作者：
Zhang, Yufeng;Yang, Haiyan;Zhang, Xianghong
长链非编码RNA（lncRNA）正在成为癌症发生和发展的关键调控因子。TP 53 TG 1是最近发现的一种lncRNA，许多研究表明TP 53 TG 1可能在不同的肿瘤中发挥抑癌基因或癌基因的作用。然而，TP 53 TG 1参与胰腺导管腺癌（PDAC）的致癌作用尚未得到表征。在我们的研究中，我们发现TP 53 TG 1在PDAC中高度表达，并且是PDAC发育的新调节因子。敲低TP 53 TG 1可抑制PDAC细胞的增殖，诱导凋亡，并降低其迁移和侵袭能力，而增强TP 53 TG 1的表达则具有相反的作用。从机制上讲，TP 53 TG 1可以直接结合microRNA（miR）-96，并有效地充当miR-96的海绵，从而拮抗miR-96的功能，并导致其内源性靶点KRAS的去抑制，KRAS是PDAC启动和维持的核心癌基因。综上所述，这些观察结果表明TP 53 TG 1通过作为竞争性内源性RNA（ceRNA）竞争性结合miR-96并调节KRAS表达而促进PDAC的生长和进展，这突出了复杂的miRNA-lncRNA网络在调节PDAC进展中的重要性。
Long noncoding RNAs (lncRNAs) are emerging as key regulators in cancer initiation and progression. TP53TG1 is a recently identified lncRNA and several studies have shown that TP53TG1 may play the role of tumor suppressor gene or oncogene in different tumors. Nevertheless, the involvement of TP53TG1 in carcinogenesis of pancreatic ductal adenocarcinoma (PDAC) has not been characterized. In our studies, we identified that TP53TG1 was highly expressed in PDAC and was a novel regulator of PDAC development. Knockdown of TP53TG1 inhibited proliferation, induced apoptosis, and decreased migration and invasion in PDAC cells, whereas enhanced expression of TP53TG1 had the opposite effects. Mechanistically, TP53TG1 could directly bind to microRNA (miR)-96 and effectively function as a sponge for miR-96, thus antagonizing the functions of miR-96 and leading to derepression of its endogenous target KRAS, which is a core oncogene in the initiation and maintenance of PDAC. Taken together, these observations imply that TP53TG1 contributes to the growth and progression of PDAC by acting as a competing endogenous RNA (ceRNA) to competitively bind to miR-96 and regulate KRAS expression, which highlights the importance of the complicated miRNA-lncRNA network in modulating the progression of PDAC.