Epigenetically associated IGF2BP3 upregulation promotes cell proliferation by regulating E2F1 expression in hepatocellular carcinoma

Chenghao Liu; Yicheng Zhuo; Xiaofeng Yang; Chen Yang; Min Shu; Bowen Hou; Jun Hou; Xueling Chen; Lianghai Wang; Xiangwei Wu

doi:10.1038/s41598-024-67021-w

Epigenetically associated IGF2BP3 upregulation promotes cell proliferation by regulating E2F1 expression in hepatocellular carcinoma

Sci Rep. 2024 Jul 11;14(1):16051. doi: 10.1038/s41598-024-67021-w.

Authors

Chenghao Liu^{1

2}, Yicheng Zhuo^{1

2}, Xiaofeng Yang^{1

2}, Chen Yang^{1

2}, Min Shu^{1

2}, Bowen Hou^{1

2}, Jun Hou^{1

2}, Xueling Chen^{1

2}, Lianghai Wang^{3

4}, Xiangwei Wu^{5

6}

Affiliations

¹ NHC Key Laboratory of Prevention and Treatment of Central Asia High Incidence Diseases, Shihezi University, Shihezi, Xinjiang, China.
² Key Laboratory of Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, Shihezi, Xinjiang, China.
³ NHC Key Laboratory of Prevention and Treatment of Central Asia High Incidence Diseases, Shihezi University, Shihezi, Xinjiang, China. lh_wang@shzu.edu.cn.
⁴ Key Laboratory of Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, Shihezi, Xinjiang, China. lh_wang@shzu.edu.cn.
⁵ NHC Key Laboratory of Prevention and Treatment of Central Asia High Incidence Diseases, Shihezi University, Shihezi, Xinjiang, China. wxwshz@126.com.
⁶ Key Laboratory of Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, Shihezi, Xinjiang, China. wxwshz@126.com.

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.

Keywords: E2F1; HCC; Methylation; Prognosis; RNA-binding protein.

MeSH terms

Biomarkers, Tumor / genetics
Biomarkers, Tumor / metabolism
Carcinoma, Hepatocellular* / genetics
Carcinoma, Hepatocellular* / metabolism
Carcinoma, Hepatocellular* / pathology
Cell Line, Tumor
Cell Proliferation* / genetics
DNA Methylation*
E2F1 Transcription Factor* / genetics
E2F1 Transcription Factor* / metabolism
Epigenesis, Genetic*
Female
Gene Expression Regulation, Neoplastic*
Hep G2 Cells
Humans
Liver Neoplasms* / genetics
Liver Neoplasms* / metabolism
Liver Neoplasms* / pathology
Male
Middle Aged
Prognosis
RNA-Binding Proteins* / genetics
RNA-Binding Proteins* / metabolism
Up-Regulation* / genetics

Substances

IGF2BP3 protein, human
RNA-Binding Proteins
E2F1 Transcription Factor
E2F1 protein, human
Biomarkers, Tumor

Abstract

MeSH terms

Substances

Grants and funding