Oral squamous cell carcinoma (OSCC) is one of the most common malignancies in the world, with a high mortality rate. RAN is a member of the Ras GTPase family and is overexpressed in a range of cancers, however, the relationship between RAN and OSCC is rarely reported. In this study, we found that RAN is overexpressed in OSCC tissues. RAN inhibition retarded OSCC cell proliferation and led to apoptosis and cell cycle arrest. Knockdown of RAN inhibited tumor growth in vivo. Strikingly, we found that RAN and oncogene Y-box binding protein-1 (YBX1) are positively associated with the immune infiltrates of CD4⁺ Th2 cells in multiple types of cancer, and can promote IL-4 expression. IL-4 treatment can partially rescue RAN knockdown-induced cell apoptosis in OSCC cells. Moreover, overexpression of RAN could rescue cell growth inhibition caused by knockdown of YBX1. Furthermore, patients with low expression of both RAN and YBX1 had better overall survival than others. Collectively, these findings indicate that RAN is a target of YBX1. RAN and YBX1 are required for cell proliferation and IL-4 expression. RAN and YBX1 are co-expressed and can serve as potential co-biomarkers for poor prognosis in OSCC.

口腔鳞状细胞癌（OSCC）是世界上最常见的恶性肿瘤之一，死亡率很高。RAN 是 Ras GTPase 家族的成员，在一系列癌症中过度表达，然而，很少报道 RAN 和 OSCC 之间的关系。在这项研究中，我们发现 RAN 在 OSCC 组织中过度表达。RAN 抑制延缓 OSCC 细胞增殖并导致细胞凋亡和细胞周期停滞。RAN 的敲低抑制了体内肿瘤的生长。引人注目的是，我们发现 RAN 和癌基因 Y-box 结合蛋白-1 (YBX1) 与 CD4 ⁺的免疫浸润呈正相关Th2细胞在多种癌症中，并能促进IL-4的表达。IL-4 治疗可以部分挽救 RAN 敲低诱导的 OSCC 细胞凋亡。此外，RAN 的过表达可以挽救 YBX1 敲低引起的细胞生长抑制。此外，RAN 和 YBX1 均低表达的患者比其他患者具有更好的总体生存率。总的来说，这些发现表明 RAN 是 YBX1 的目标。RAN 和 YBX1 是细胞增殖和 IL-4 表达所必需的。RAN 和 YBX1 共表达，可作为 OSCC 不良预后的潜在联合生物标志物。