The long noncoding RNA ELFN1-AS1 promotes gastric cancer growth and metastasis by interacting with TAOK1 to inhibit the Hippo signaling pathway.

IF 6.1 2区生物学 Q1 CELL BIOLOGY

Cell Death Discovery Pub Date : 2024-11-11 DOI:10.1038/s41420-024-02235-5

Yuanhang Wang, Kuan Shen, Quan Cheng, Xinyi Zhou, Kanghui Liu, Jian Xiao, Li Hu

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Abstract

Gastric cancer (GC) is a common digestive malignancy that causes numerous cancer-related deaths. Long noncoding RNAs (lncRNAs) play a crucial role in the development of various tumors, including GC. In this study, we revealed that ELFN1-AS1, a lncRNA with aberrantly high expression, contributes to the proliferation and metastasis of GC. Mechanically, ELFN1-AS1 plays an oncogenic role by binding to the protein kinase domain of thousand and one amino acid protein kinase (TAOK1), a tumor suppressor in GC, and disrupting the TAOK1-STK3 interaction, leading to decreased STK3 phosphorylation. This decrease is accompanied by attenuation of the Hippo kinase cascade, resulting in reduced YAP1 phosphorylation, a crucial effector of the Hippo signaling pathway. Subsequently, the reduced YAP1 phosphorylation promotes its nuclear translocation, thereby enhancing the expression of MYC, a downstream target of the pathway and well-known oncogene. Taken together, the ELFN1-AS1/TAOK1/STK3/YAP1 axis may promote GC progression and is a promising target for GC treatment.

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长非编码 RNA ELFN1-AS1 通过与 TAOK1 相互作用抑制 Hippo 信号通路，从而促进胃癌的生长和转移。

胃癌（GC）是一种常见的消化系统恶性肿瘤，导致大量癌症相关死亡。长非编码 RNA（lncRNA）在各种肿瘤（包括胃癌）的发生发展中起着至关重要的作用。在这项研究中，我们发现了一种异常高表达的lncRNA--ELFN1-AS1，它有助于GC的增殖和转移。在机制上，ELFN1-AS1通过与GC的肿瘤抑制因子千分之一氨基酸蛋白激酶（TAOK1）的蛋白激酶结构域结合，破坏TAOK1-STK3的相互作用，导致STK3磷酸化减少，从而发挥致癌作用。STK3 磷酸化的减少伴随着 Hippo 激酶级联的减弱，导致 Hippo 信号通路的关键效应因子 YAP1 磷酸化减少。随后，YAP1 磷酸化的减少促进了它的核转位，从而增强了该通路的下游靶标和众所周知的致癌基因 MYC 的表达。综上所述，ELFN1-AS1/TAOK1/STK3/YAP1 轴可能会促进 GC 的进展，是治疗 GC 的一个有希望的靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cell Death Discovery Biochemistry, Genetics and Molecular Biology-Cell Biology

CiteScore

8.30

自引率

1.40%

发文量

468

审稿时长

9 weeks

期刊介绍： Cell Death Discovery is a multidisciplinary, international, online-only, open access journal, dedicated to publishing research at the intersection of medicine with biochemistry, pharmacology, immunology, cell biology and cell death, provided it is scientifically sound. The unrestricted access to research findings in Cell Death Discovery will foster a dynamic and highly productive dialogue between basic scientists and clinicians, as well as researchers in industry with a focus on cancer, neurobiology and inflammation research. As an official journal of the Cell Death Differentiation Association (ADMC), Cell Death Discovery will build upon the success of Cell Death & Differentiation and Cell Death & Disease in publishing important peer-reviewed original research, timely reviews and editorial commentary. Cell Death Discovery is committed to increasing the reproducibility of research. To this end, in conjunction with its sister journals Cell Death & Differentiation and Cell Death & Disease, Cell Death Discovery provides a unique forum for scientists as well as clinicians and members of the pharmaceutical and biotechnical industry. It is committed to the rapid publication of high quality original papers that relate to these subjects, together with topical, usually solicited, reviews, editorial correspondence and occasional commentaries on controversial and scientifically informative issues.