Hepatocellular carcinoma (HCC) is one of the most deadly malignant cancers worldwide. Research into the crucial genes responsible for maintaining the aggressive behaviour of cancer cells is important for the clinical treatment of HCC. The purpose of this study was to determine whether the E3 ubiquitin ligase Ring Finger Protein 125 (RNF125) plays a role in the proliferation and metastasis of HCC. RNF125 expression in human HCC samples and cell lines was investigated using TCGA dataset mining, qRT‒PCR, western blot, and immunohistochemistry assays. In addition, 80 patients with HCC were studied for the clinical value of RNF125. Furthermore, the molecular mechanism by which RNF125 contributes to hepatocellular carcinoma progression was determined with mass spectrometry (MS), coimmunoprecipitation (Co-IP), dual-luciferase reporter assays, and ubiquitin ladder assays. We found that RNF125 was markedly downregulated in HCC tumour tissues, which was associated with a poor prognosis for patients with HCC. Moreover, the overexpression of RNF125 inhibited HCC proliferation and metastasis both in vitro and in vivo, whereas the knockdown of RNF125 exerted antithetical effects. Mechanistically, mass spectrometry analysis revealed a protein interaction between RNF125 and SRSF1, and RNF125 accelerated the proteasome-mediated degradation of SRSF1, which impeded HCC progression by inhibiting the ERK signalling pathway. Furthermore, RNF125 was detected to be the downstream target of miR-103a-3p. In this study, we identified that RNF125 is a tumour suppressor in HCC and inhibits HCC progression by inhibiting the SRSF1/ERK pathway. These findings provide a promising treatment target for HCC.

肝细胞癌（HCC）是全世界最致命的恶性肿瘤之一。研究负责维持癌细胞侵袭行为的关键基因对于 HCC 的临床治疗具有重要意义。本研究的目的是确定E3泛素连接酶环指蛋白125（RNF125）是否在HCC的增殖和转移中发挥作用。使用 TCGA 数据集挖掘、qRT-PCR、蛋白质印迹和免疫组织化学测定研究人类 HCC 样本和细胞系中的 RNF125 表达。此外，还研究了 80 名 HCC 患者 RNF125 的临床价值。此外，通过质谱 (MS)、免疫共沉淀 (Co-IP)、双荧光素酶报告基因检测确定了 RNF125 促进肝细胞癌进展的分子机制，和泛素阶梯分析。我们发现RNF125在HCC肿瘤组织中显着下调，这与HCC患者的不良预后相关。此外，RNF125的过表达在体外和体内均抑制HCC增殖和转移，而RNF125的敲低则产生相反的作用。从机制上讲，质谱分析揭示了 RNF125 和 SRSF1 之间的蛋白质相互作用，并且 RNF125 加速了蛋白酶体介导的 SRSF1 降解，从而通过抑制 ERK 信号通路来阻止 HCC 进展。此外，RNF125 被检测为 miR-103a-3p 的下游靶标。在这项研究中，我们发现 RNF125 是 HCC 中的肿瘤抑制因子，并通过抑制 SRSF1/ERK 通路来抑制 HCC 进展。这些发现为 HCC 提供了有希望的治疗靶点。