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Abstract：
RNA-binding proteins (RBPs) are a class of proteins that primarily function by interacting with different types of RNAs and play a critical role in regulating the transcription and translation of cancer-related genes. However, their role in the progression of hepatocellular carcinoma (HCC) remains unclear. In this study, we analyzed RNA sequencing data and the corresponding clinical information of patients with HCC to screen for prognostic RBPs. Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) was identified as an independent prognostic factor for liver cancer. It is upregulated in HCC and is associated with a poor prognosis. Elevated IGF2BP3 expression was validated via immunohistochemical analysis using a tissue microarray of patients with HCC. IGF2BP3 knockdown inhibited the proliferation of Hep3B and HepG2 cells, whereas IGF2BP3 overexpression promoted the expansion of HuH-7 and MHCC97H cells. Mechanistically, IGF2BP3 modulates cell proliferation by regulating E2F1 expression. DNA hypomethylation of the IGF2BP3 gene may increase the expression of IGF2BP3, thereby enhancing cell proliferation in HCC. Therefore, IGF2BP3 may act as a novel prognostic biomarker and a potential therapeutic target for HCC.
摘要：
RNA结合蛋白（RBP）是一类主要通过与不同类型的RNA相互作用而起作用的蛋白质，并在调节癌症相关基因的转录和翻译中起关键作用。然而,它们在肝细胞癌（HCC）进展中的作用尚不清楚。在这项研究中,我们分析了肝癌患者的RNA测序数据和相应的临床信息,以筛选预后RBPs.胰岛素样生长因子2mRNA结合蛋白3（IGF2BP3）被确定为肝癌的独立预后因素。它在HCC中上调，并与不良预后相关。通过使用HCC患者的组织微阵列的免疫组织化学分析来验证IGF2BP3表达的升高。IGF2BP3敲低抑制Hep3B和HepG2细胞增殖,而IGF2BP3过表达促进HuH-7和MHCC97H细胞的扩增。机械上,IGF2BP3通过调节E2F1表达来调节细胞增殖。IGF2BP3基因的DNA低甲基化可能会增加IGF2BP3的表达，从而增强HCC的细胞增殖。因此,IGF2BP3可能作为一个新的预后生物标志物和肝癌的潜在治疗靶点。
