表观遗传学相关的 IGF2BP3 上调通过调节肝细胞癌中 E2F1 的表达来促进细胞增殖。
Epigenetically associated IGF2BP3 upregulation promotes cell proliferation by regulating E2F1 expression in hepatocellular carcinoma.
发表日期:2024 Jul 11
作者:
Chenghao Liu, Yicheng Zhuo, Xiaofeng Yang, Chen Yang, Min Shu, Bowen Hou, Jun Hou, Xueling Chen, Lianghai Wang, Xiangwei Wu
来源:
Epigenetics & Chromatin
摘要:
RNA结合蛋白(RBP)是一类主要通过与不同类型的RNA相互作用发挥作用的蛋白质,在调节癌症相关基因的转录和翻译中发挥着关键作用。然而,它们在肝细胞癌(HCC)进展中的作用仍不清楚。在本研究中,我们分析了 HCC 患者的 RNA 测序数据和相应的临床信息,以筛选预后 RBP。胰岛素样生长因子 2 mRNA 结合蛋白 3 (IGF2BP3) 被确定为肝癌的独立预后因素。它在 HCC 中表达上调,并与不良预后相关。使用 HCC 患者的组织微阵列通过免疫组织化学分析验证 IGF2BP3 表达升高。 IGF2BP3敲低抑制Hep3B和HepG2细胞的增殖,而IGF2BP3过表达促进HuH-7和MHCC97H细胞的扩增。从机制上讲,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 中的细胞增殖。因此,IGF2BP3 可能作为 HCC 的新型预后生物标志物和潜在治疗靶点。© 2024。作者。
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.© 2024. The Author(s).