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TGF-β 诱导的 LINC00152 通过 HuR 促进肺腺癌转移。

LINC00152 induced by TGF-β promotes metastasis via HuR in lung adenocarcinoma.

机构信息

NHC Key Laboratory of Carcinogenesis, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China.

Academy of Medical Science, Zhengzhou University, Zhengzhou, Henan, China.

出版信息

Cell Death Dis. 2022 Sep 7;13(9):772. doi: 10.1038/s41419-022-05164-2.

Abstract

Lung adenocarcinoma (LUAD) is one of the main causes of cancer-related mortality, with a strong tendency to metastasize early. Transforming growth factor-β (TGF-β) signaling is a powerful regulator to promote metastasis of LUAD. Here, we screened long non-coding RNAs (lncRNAs) responsive to TGF-β and highly expressed in LUAD cells, and finally obtained our master molecular LINC00152. We proved that the TGF-β promoted transcription of LINC00152 through the classical TGF-β/SMAD3 signaling pathway and maintained its stability through the RNA-binding protein HuR. Moreover, LINC00152 increased ZEB1, SNAI1 and SNAI2 expression via increasing the interactions of HuR and these transcription factors, ultimately promoting epithelial-mesenchymal transition of LUAD cell and enhancing LUAD metastasis in vivo. These data provided evidence that LINC00152 induced by TGF-β promotes metastasis depending HuR in lung adenocarcinoma. Designing targeting LINC00152 and HuR inhibitors may therefore be an effective therapeutic strategy for LUAD treatment.

摘要

肺腺癌 (LUAD) 是癌症相关死亡的主要原因之一,具有早期转移的强烈倾向。转化生长因子-β (TGF-β) 信号是促进 LUAD 转移的强大调节剂。在这里,我们筛选了对 TGF-β有反应且在 LUAD 细胞中高表达的长非编码 RNA (lncRNA),并最终获得了我们的主要分子 LINC00152。我们证明 TGF-β 通过经典的 TGF-β/SMAD3 信号通路促进 LINC00152 的转录,并通过 RNA 结合蛋白 HuR 维持其稳定性。此外,LINC00152 通过增加 HuR 和这些转录因子之间的相互作用来增加 ZEB1、SNAI1 和 SNAI2 的表达,最终促进 LUAD 细胞的上皮-间充质转化,并增强 LUAD 体内转移。这些数据提供了证据,表明 TGF-β 诱导的 LINC00152 通过 HuR 促进肺腺癌的转移。因此,设计针对 LINC00152 和 HuR 的抑制剂可能是 LUAD 治疗的有效治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f809/9452677/e1e1e17b1361/41419_2022_5164_Fig1_HTML.jpg

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