YTHDC1 promotes the malignant progression of gastric cancer by promoting ROD1 translocation to the nucleus

IF 5.3 2区医学 Q2 CELL BIOLOGY Cell Biology and Toxicology Pub Date : 2024-04-04 DOI:10.1007/s10565-024-09859-4

Danhong Dong, Jiangpeng Wei, Weidong Wang, Haikun Zhou, Liu Hong, Gang Ji, Xisheng Yang

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Abstract

RNA-binding proteins (RBPs) make vital impacts on tumor progression and are important potential targets for tumor treatment. Previous studies have shown that RBP regulator of differentiation 1 (ROD1), enriched in the nucleus, is abnormally expressed and functions as a splicing factor in tumors; however, the mechanism underlying its involvement in gastric cancer (GC) is unknown. In this study, ROD1 is found to stimulate GC cell proliferation and metastasis and is related to poor patient prognosis. In vitro experiments showed that ROD1 influences GC proliferation and metastasis through modulating the imbalance of the level of the oncogenic gene OIP5 and the tumor suppressor gene GPD1L. Further studies showed that the N6-methyladenosine (m6A) “reader” protein YTHDC1 can interact with ROD1 and regulate the balance of the expression of the downstream molecules OIP5/GPD1L by promoting the nuclear enrichment of ROD1. Therefore, YTHDC1 stimulates GC development and progression through modulating nuclear enrichment of the splicing factor ROD1.

Graphical Abstract

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YTHDC1 通过促进 ROD1 转位至细胞核来推动胃癌的恶性进展

RNA 结合蛋白（RBPs）对肿瘤的进展有重要影响，是治疗肿瘤的重要潜在靶点。以往的研究表明，RBP 分化调节因子 1（ROD1）富集于细胞核中，在肿瘤中异常表达并作为剪接因子发挥作用；然而，其参与胃癌（GC）的机制尚不清楚。本研究发现，ROD1 能刺激胃癌细胞增殖和转移，并与患者的不良预后有关。体外实验表明，ROD1通过调节致癌基因OIP5和抑癌基因GPD1L的水平失衡来影响GC细胞的增殖和转移。进一步的研究表明，N6-甲基腺苷（m6A）"阅读器 "蛋白YTHDC1能与ROD1相互作用，并通过促进ROD1的核富集来调节下游分子OIP5/GPD1L的表达平衡。因此，YTHDC1通过调节剪接因子ROD1的核富集来刺激GC的发育和进展。

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来源期刊

Cell Biology and Toxicology 生物-毒理学

CiteScore

9.90

自引率

4.90%

发文量

101

审稿时长

>12 weeks

期刊介绍： Cell Biology and Toxicology (CBT) is an international journal focused on clinical and translational research with an emphasis on molecular and cell biology, genetic and epigenetic heterogeneity, drug discovery and development, and molecular pharmacology and toxicology. CBT has a disease-specific scope prioritizing publications on gene and protein-based regulation, intracellular signaling pathway dysfunction, cell type-specific function, and systems in biomedicine in drug discovery and development. CBT publishes original articles with outstanding, innovative and significant findings, important reviews on recent research advances and issues of high current interest, opinion articles of leading edge science, and rapid communication or reports, on molecular mechanisms and therapies in diseases.