STRIP2 motivates non-small cell lung cancer progression by modulating the TMBIM6 stability through IGF2BP3 dependent.
STRIP2 motivates non-small cell lung cancer progression by modulating the TMBIM6 stability through IGF2BP3 dependent.
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STRIP2 通过 IGF2BP3 依赖性调节 TMBIM6 稳定性来促进非小细胞肺癌进展
DOI：
10.1186/s13046-022-02573-1
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发表时间：
2023-01-13
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Striatin Interaction Protein 2(STRIP2)是STRIPAK复合体的核心成分，通过调节细胞收缩和转移参与肿瘤的发生和发展。然而，STRIP2在非小细胞肺癌(NSCLC)进展中的潜在分子机制在很大程度上仍不清楚。采用定量RT-PCR、Western blotting和免疫组织化学(IHC)方法检测STRIP2和IGF2BP3在人NSCLC标本和NSCLC细胞系中的表达。在体内外研究了STRIP2在促进NSCLC进展中的作用及其分子机制。在此，我们发现STRIP2在非小细胞肺癌组织中的表达显著升高，并且高表达与预后不良相关。STRIP2基因的敲除在体内外均能抑制肿瘤的生长和转移，而过表达的STRIP2则起到相反的作用。机制上，P300/CBP介导的STRIP2启动子H3K27乙酰化激活可诱导STRIP2转录，并与胰岛素样生长因子2mRNA结合蛋白3(IGF2BP3)相互作用，上调IGF2BP3转录。此外，STRIP2-IGF2BP3轴刺激TMBIM6mRNA的m6A修饰，增强TMBIM6的稳定性。因此，TMBIM6依赖于STRIP2和IGF2BP3参与NSCLC细胞的增殖、迁移和侵袭。在NSCLC患者中，STRIP2、IGF2BP3和TMBIM6的高共表达与不良预后相关。我们的研究结果表明，STRIP2与IGF2BP3相互作用，以m6A依赖的方式调节TMBIM6mRNA的稳定性，可能是一种潜在的NSCLC预后生物标志物和治疗靶点。网上版载有补充材料，可在10.1186/s13046-022-02573-1查阅。
Striatin interacting protein 2 (STRIP2) is a core component of the striatin-interacting phosphatase and kinase (STRIPAK) complexes, which is involved in tumor initiation and progression via the regulation of cell contractile and metastasis. However, the underlying molecular mechanisms of STRIP2 in non-small cell lung cancer (NSCLC) progression remain largely unknown. The expressions of STRIP2 and IGF2BP3 in human NSCLC specimens and NSCLC cell lines were detected using quantitative RT-PCR, western blotting, and immunohistochemistry (IHC) analyses. The roles and molecular mechanisms of STRIP2 in promoting NSCLC progression were investigated in vitro and in vivo. Here, we found that STRIP2 expression was significantly elevated in NSCLC tissues and high STRIP2 expression was associated with a poor prognosis. Knockdown of STRIP2 suppressed tumor growth and metastasis in vitro and in vivo, while STRIP2 overexpression obtained the opposite effect. Mechanistically, P300/CBP-mediated H3K27 acetylation activation in the promoter of STRIP2 induced STRIP2 transcription, which interacted with insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) and upregulated IGF2BP3 transcription. In addition, STRIP2-IGF2BP3 axis stimulated m6A modification of TMBIM6 mRNA and enhanced TMBIM6 stability. Consequently, TMBIM6 involved NSCLC cell proliferation, migration and invasion dependent on STRIP2 and IGF2BP3. In NSCLC patients, high co-expression of STRIP2, IGF2BP3 and TMBIM6 was associated with poor outcomes. Our findings indicate that STRIP2 interacts with IGF2BP3 to regulate TMBIM6 mRNA stability in an m6A-dependent manner and may represent a potential prognostic biomarker and therapeutic target for NSCLC. The online version contains supplementary material available at 10.1186/s13046-022-02573-1.
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影响因子：
16.8
作者：
Jeong BC;Bae SJ;Ni L;Zhang X;Bai XC;Luo X
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