背景:已广泛研究了膜相关RING-CH(MARCH)家族在致癌作用中的作用,但是这个家族的成员,RNF173尚未在肝细胞癌(HCC)的背景下进行彻底探索。
方法:使用HCC组织微阵列和IHC染色,我们旨在确定RNF173在HCC患者中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。RNA测序,质谱,并进行免疫沉淀以揭示RNF173对HCC发展的影响的潜在机制。
结果:HCC组织中RNF173的mRNA和蛋白水平明显低于正常组织。低RNF173表达的HCC患者总生存期和无复发生存期较短,RNF173与肿瘤数量显著相关,肿瘤包膜,肿瘤分化,和BCLC阶段。此外,体外和体内实验表明,RNF173的下调加剧了肿瘤的进展,包括迁移,入侵,和扩散。GRB2是RAF/MEK/ERK途径中的关键分子。RNF173通过泛素化和降解GRB2抑制RAF/MEK/ERK信号传导,从而抑制HCC细胞增殖,入侵和迁移。结合临床样本,我们发现RNF173高表达和GRB2低表达的HCC患者预后最好.
结论:RNF173通过泛素化和降解GRB2抑制HCC的侵袭和转移,从而抑制RAF/MEK/ERK信号通路。RNF173是HCC患者生存和复发的独立危险因素。RNF173可作为HCC的一个新的预后分子和潜在的治疗靶点。RAF/MEK/ERK信令上的RNF173的视频抽象图形抽象模型。RNF173敲低导致GRB2的泛素化和降解受损,导致RAF/MEK/ERK信号通路的激活,促进HCC细胞的侵袭和转移。
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.