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

中文翻译：

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YTHDC1通过促进ROD1转入细胞核促进胃癌恶性进展

RNA结合蛋白（RBP）对肿瘤进展产生重要影响，是肿瘤治疗的重要潜在靶标。先前的研究表明，细胞核中富集的 RBP 分化调节因子 1 (ROD1) 异常表达，并在肿瘤中充当剪接因子。然而，其参与胃癌（GC）的机制尚不清楚。在这项研究中，发现 ROD1 会刺激 GC 细胞增殖和转移，并与患者不良预后相关。体外实验表明，ROD1通过调节致癌基因OIP5和抑癌基因GPD1L水平的失衡来影响GC增殖和转移。进一步研究表明，N6-甲基腺苷（m6A）“阅读器”蛋白YTHDC1可以与ROD1相互作用，通过促进ROD1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 的发生和进展。

图形概要