LncRNA-PAGBC 通过充当 microRNA 海绵促进胆囊肿瘤发生。
LncRNA-PAGBC acts as a microRNA sponge and promotes gallbladder tumorigenesis.
机构信息
Department of General Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Shanghai Research Center of Biliary Tract Disease, Shanghai, China.
出版信息
EMBO Rep. 2017 Oct;18(10):1837-1853. doi: 10.15252/embr.201744147. Epub 2017 Sep 8.
Long noncoding RNAs (lncRNAs) play roles in the development and progression of many cancers; however, the contributions of lncRNAs to human gallbladder cancer (GBC) remain largely unknown. In this study, we identify a group of differentially expressed lncRNAs in human GBC tissues, including prognosis-associated gallbladder cancer lncRNA (lncRNA-PAGBC), which we find to be an independent prognostic marker in GBC Functional analysis indicates that lncRNA-PAGBC promotes tumour growth and metastasis of GBC cells. More importantly, as a competitive endogenous RNA (ceRNA), lncRNA-PAGBC competitively binds to the tumour suppressive microRNAs miR-133b and miR-511. This competitive role of lncRNA-PAGBC is required for its ability to promote tumour growth and metastasis and to activate the AKT/mTOR pathway. Moreover, lncRNA-PAGBC interacts with polyadenylate binding protein cytoplasmic 1 (PABPC1) and is stabilized by this interaction. This work provides novel insight on the molecular pathogenesis of GBC.
长链非编码 RNA（lncRNAs）在许多癌症的发生和发展中发挥作用；然而，lncRNAs 对人类胆囊癌（GBC）的贡献在很大程度上仍不清楚。在这项研究中，我们鉴定了一组在人 GBC 组织中差异表达的 lncRNAs，包括与预后相关的胆囊癌 lncRNA（lncRNA-PAGBC），我们发现其是 GBC 的独立预后标志物。功能分析表明，lncRNA-PAGBC 促进 GBC 细胞的肿瘤生长和转移。更重要的是，作为竞争性内源性 RNA（ceRNA），lncRNA-PAGBC 竞争性结合肿瘤抑制性 microRNAs miR-133b 和 miR-511。lncRNA-PAGBC 的这种竞争作用对于其促进肿瘤生长和转移以及激活 AKT/mTOR 通路是必需的。此外，lncRNA-PAGBC 与多聚腺苷酸结合蛋白细胞质 1（PABPC1）相互作用并通过这种相互作用得到稳定。这项工作为 GBC 的分子发病机制提供了新的见解。
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