State Key Laboratory of Medical Proteomics, National Center for Protein Sciences (Beijing), Beijing Proteome Research Center, Beijing Institute of Lifeomics, Beijing 102206, China.
Anhui Medical University, Hefei 230032, China.
J Proteome Res. 2024 Oct 4;23(10):4553-4566. doi: 10.1021/acs.jproteome.4c00457. Epub 2024 Aug 30.
Hepatocellular carcinoma (HCC) is a highly lethal cancer, and proteomic studies have shown increased protein diversity and abundance in HCC tissues, whereas the role of protein translation has not been extensively explored in HCC. Our research focused on key molecules in the translation process to identify a potential contributor in HCC. We discovered that EIF4G2, a crucial translation initiation factor, is significantly upregulated in HCC tissues and associated with poor prognosis. This study uniquely highlights the impact of EIF4G2 deletion, which suppresses tumor growth and metastasis both in and in . Furthermore, polysome analysis and nascent protein synthesis assays revealed EIF4G2's role in regulating protein translation, specifically identifying PLEKHA1 as a key translational product. This represents a novel mechanistic insight into HCC malignancy. RNA immunoprecipitation (RIP) and Dual-luciferase reporter assays further revealed that EIF4G2 facilitates PLEKHA1 translation via an IRES-dependent manner. Importantly, the synergistic effects of EIF4G2 depletion and PLEKHA1 reduction in inhibiting cell migration and invasion underscore the therapeutic potential of targeting this axis. This study not only advances our understanding of translational regulation in HCC but also identifies the EIF4G2-PLEKHA1 axis as a promising therapeutic target, offering new avenues for intervention in HCC treatment.
肝细胞癌 (HCC) 是一种高度致命的癌症，蛋白质组学研究表明 HCC 组织中蛋白质的多样性和丰度增加，而蛋白质翻译在 HCC 中的作用尚未得到广泛探索。我们的研究集中在翻译过程中的关键分子上，以确定 HCC 中的一个潜在贡献者。我们发现，EIF4G2，一种至关重要的翻译起始因子，在 HCC 组织中显著上调，并与预后不良相关。这项研究独特地强调了 EIF4G2 缺失的影响，它不仅在体内，而且在异种移植模型中均抑制肿瘤生长和转移。此外，多核糖体分析和新生蛋白合成测定揭示了 EIF4G2 在调节蛋白质翻译中的作用，特别是鉴定 PLEKHA1 是一个关键的翻译产物。这代表了对 HCC 恶性的一种新的机制见解。RNA 免疫沉淀 (RIP) 和双荧光素酶报告基因测定进一步表明，EIF4G2 通过 IRES 依赖性方式促进 PLEKHA1 的翻译。重要的是，EIF4G2 耗竭和 PLEKHA1 减少协同抑制细胞迁移和侵袭，突出了靶向该轴的治疗潜力。这项研究不仅提高了我们对 HCC 翻译调控的理解，而且还确定了 EIF4G2-PLEKHA1 轴作为一个有前途的治疗靶点，为 HCC 治疗提供了新的干预途径。
