膜相关的RING-CH（MARCH）家族在癌症发生中的作用已得到广泛研究，但该家族成员RNF173在肝细胞癌（HCC）的背景下尚未得到充分探讨。通过使用HCC组织微阵列和免疫组化染色，我们旨在确定HCC患者中RNF173的差异表达及其临床意义。通过体外和体内实验研究了RNF173的生物学作用。通过RNA测序、质谱和免疫沉淀等方法，揭示了RNF173对HCC发展的潜在机制。在HCC组织中，RNF173的mRNA和蛋白水平明显低于正常组织。RNF173表达低的HCC患者具有更短的总生存期和无复发生存期，并且RNF173与肿瘤数量、肿瘤包膜、肿瘤分化和BCLC分期显著相关。此外，体外和体内实验表明，RNF173的下调加重了肿瘤的进展，包括迁移、侵袭和增殖。GRB2是RAF/MEK/ERK信号通路中的关键分子。RNF173通过泛素化和降解GRB2来抑制RAF/MEK/ERK信号通路，从而抑制HCC细胞的增殖、侵袭和迁移。结合临床样本，我们发现RNF173高表达和GRB2低表达的HCC患者具有最佳预后。RNF173通过泛素化和降解GRB2来抑制HCC的侵袭和转移，从而抑制RAF/MEK/ERK信号通路。RNF173是HCC患者存活和复发的独立风险因子。RNF173可能作为HCC的新预后分子和潜在治疗靶点。视频摘要 图表摘要 RNF173对RAF/MEK/ERK信号通路的作用模型。RNF173敲除导致GRB2泛素化和降解受损，从而激活RAF/MEK/ERK信号通路，促进HCC细胞的侵袭和转移。© 2023. BioMed Central Ltd., part of Springer Nature.

The role of the membrane-associated RING-CH (MARCH) family in carcinogenesis has been widely studied, but the member of this family, RNF173, has not yet been thoroughly explored in the context of hepatocellular carcinoma (HCC).With the use of an HCC tissue microarray and IHC staining, we aim to determine the differential expression of RNF173 in HCC patients and its clinical significance. The biological role of RNF173 is investigated through in vitro and in vivo experiments. RNA sequencing, mass spectrometry, and immunoprecipitation are performed to uncover the underlying mechanism of RNF173's impact on the development of HCC.The mRNA and protein levels of RNF173 were significantly lower in HCC tissues than in normal tissues. HCC patients with low RNF173 expression had shorter overall survival and recurrence-free survival, and RNF173 was significantly correlated with tumor number, tumor capsule, tumor differentiation, and BCLC stage. In addition, in vitro and in vivo experiments showed that RNF173 downregulation exacerbated tumor progression, including migration, invasion, and proliferation. GRB2 is a key molecule in the RAF/MEK/ERK pathway. RNF173 inhibits the RAF/MEK/ERK signaling by ubiquitinating and degrading GRB2, thereby suppressing HCC cell proliferation, invasion and migration. Combining clinical samples, we found that HCC patients with high RNF173 and low GRB2 expression had the best prognosis.RNF173 inhibits the invasion and metastasis of HCC by ubiquitinating and degrading GRB2, thereby suppressing the RAF/MEK/ERK signaling pathway. RNF173 is an independent risk factor for the survival and recurrence of HCC patients. RNF173 may serve as a novel prognostic molecule and potential therapeutic target for HCC. Video Abstract Graphical abstract Model of RNF173 on RAF/MEK/ERK signaling. RNF173 knockdown resulted in impaired ubiquitination and degradation of GRB2, leading to the activation of the RAF/MEK/ERK signaling pathway and promotion of invasion and metastasis in HCC cells.© 2023. BioMed Central Ltd., part of Springer Nature.