IGF2BP2 Promotes Liver Cancer Growth Through an m6A-FEN1-Dependent Mechanism

Pu, Jian; Wang, Jianchu; Qin, Zebang; Wang, An Min; Zhang, Ya; Wu, Xianjian; Wu, Yi; Li, Wenchuan; Xu, Zuoming; Yuan, Linhong; Tang, Qianli; Wei, Huamei

doi:10.3389/fonc.2020.578816

Cited by 95 publications

(74 citation statements)

References 32 publications

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“…In recent years, over-expression of IGF2BP2 in multiple human cancers has been associated with poorer prognosis of the disease. For instance, over-expression of IGF2BP2 confers shorter survival and poor prognosis of patients with acute myelocytic leukemia (AML) [ 65 ], breast cancer [ 14 ], esophageal carcinoma [ 16 ], low-grade gliomas [ 17 ], hepatocellular carcinoma (HCC) [ 66 ], head and neck squamous cell carcinoma (HNSCC) [ 67 ], pancreatic ductal adenocarcinoma (PDAC) [ 20 , 68 – 70 ] and gallbladder carcinoma (GBC) [ 71 ]. Herein, we summarize the specific roles of IGF2BP2 in multiple cancers and provide a comprehensive view of IGF2BP2 (Fig.…”

Section: Igf2bp2 and Cancersmentioning

confidence: 99%

“…On the other hand, flap endonuclease-1 (FEN1), a multifunctional structure-specific nuclease critical in maintaining normal cell growth, is up-regulated in HCC [ 93 , 94 ]. Pu et al [ 66 ] reported that over-expression of IGF2BP2 promotes proliferation of HCC both in vitro and in vivo. Mechanistically, IGF2BP2 directly binds the m6A site on FEN1 mRNA, stabilizing the mRNA.…”

Section: Igf2bp2 and Cancersmentioning

confidence: 99%

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The role of IGF2BP2, an m6A reader gene, in human metabolic diseases and cancers

2021

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The human insulin-like growth factor 2 (IGF2) mRNA binding proteins 2 (IGF2BP2/IMP2) is an RNA-binding protein that regulates multiple biological processes. Previously, IGF2BP2 was thought to be a type 2 diabetes (T2D)-associated gene. Indeed IGF2BP2 modulates cellular metabolism in human metabolic diseases such as diabetes, obesity and fatty liver through post-transcriptional regulation of numerous genes in multiple cell types. Emerging evidence shows that IGF2BP2 is an N6-methyladenosine (m6A) reader that participates in the development and progression of cancers by communicating with different RNAs such as microRNAs (miRNAs), messenger RNAs (mRNAs) and long non-coding RNAs (lncRNAs). Additionally, IGF2BP2 is an independent prognostic factor for multiple cancer types. In this review, we summarize the current knowledge on IGF2BP2 with regard to diverse human metabolic diseases and its potential for cancer prognosis.

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Section: Igf2bp2 and Cancersmentioning

confidence: 99%

Section: Igf2bp2 and Cancersmentioning

confidence: 99%

The role of IGF2BP2, an m6A reader gene, in human metabolic diseases and cancers

2021

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“…It was discovered that the copy number of IGF2BP2 in tumor tissues was higher than that in adjacent normal tissues. IGF2BP2 expression promotes HCC cell proliferation in vitro and in vivo [27] . IGF2BP2 may play an oncogenic role in promoting tumor growth by inhibiting the tumor immune response reported in SCCHN [28] .…”

Section: Discussionmentioning

confidence: 99%

IGF2BP2 Promotes the Proliferation, Invasion and Migration of Esophageal Carcinoma Cells via Activation of the PI3K/AKT/EMT Signaling Pathway

Shu

Lin

Yan

et al. 2021

Preprint

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BackgroundInsulin-like growth factor 2 (IGF2) mRNA-binding protein 2 (IGF2BP2), as a m6A “reader”, is known to be an oncogene, and its expression is elevated in multiple tumors. However, the role of IGF2PB2 in esophageal squamous cell carcinoma (ESCC) is still unclear. MethodsThis study aims to investigate the role of IGF2PB2 expression in ESCC proliferation, invasion and migration as well as the possible mechanism. IGF2BP2 expression was found to be elevated in ESCC tissues by qRT-PCR, western blotting, and immunohistochemical (IHC) staining. ResultsKnocking down IGF2BP2 expression prevented the proliferation, invasion, migration and epithelial-mesenchymal transition (EMT) of KYSE450 and TE1 cells. Knocking out IGF2BP2 reduced tumorigenesis in vivo. Overexpression of IGF2BP2 was performed, and it was proven that IGF2BP2 had an oncogenic effect in KYSE450 and TE1 cells. Moreover, LY294002, a highly selective inhibitor of PI3K, reversed the effect of IGF2BP2 overexpression on EMT processes. All these results show that the effects of IGF2BP2 on oncogenesis and EMT were clearly exerted via the PI3K/AKT signaling pathway. ConclusionsIn conclusion, this study demonstrates that the oncogenic function of IGF2BP2 is mediated by the PI3K/AKT signaling pathway and is related to EMT in ESCC. In addition, IGF2BP2 can serve as a diagnostic and oncotherapeutic marker in further studies.

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“…FEN1 is essential in maintaining genome stability, replication and repair [ 79 , 80 ]. It plays a major role in DNA replication and protection against apoptosis and the development of drug resistance [ 81 ], has been suggested as a potential target in a variety of cancers [ 82 ], and has also been identified as a potential hub gene in hepatocellular carcinoma [ 75 , 83 ]. BIRC5 which is secreted into the microenvironment [ 84 ], acts as an apoptosis inhibitor [ 85 ] and may play a significant role in the apoptosis-resistant phenotype observed in TEC [ 20 ].…”

Section: Discussionmentioning

confidence: 99%

Systematic Analysis of the Transcriptome Profiles and Co-Expression Networks of Tumour Endothelial Cells Identifies Several Tumour-Associated Modules and Potential Therapeutic Targets in Hepatocellular Carcinoma

Mohr

Katz²,

Paulitschke

et al. 2021

Cancers

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Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third most common cause of cancer-related death, with tumour associated liver endothelial cells being thought to be major drivers in HCC progression. This study aims to compare the gene expression profiles of tumour endothelial cells from the liver with endothelial cells from non-tumour liver tissue, to identify perturbed biologic functions, co-expression modules, and potentially drugable hub genes that could give rise to novel therapeutic targets and strategies. Gene Set Variation Analysis (GSVA) showed that cell growth-related pathways were upregulated, whereas apoptosis induction, immune and inflammatory-related pathways were downregulated in tumour endothelial cells. Weighted Gene Co-expression Network Analysis (WGCNA) identified several modules strongly associated to tumour endothelial cells or angiogenic activated endothelial cells with high endoglin (ENG) expression. In tumour cells, upregulated modules were associated with cell growth, cell proliferation, and DNA-replication, whereas downregulated modules were involved in immune functions, particularly complement activation. In ENG+ cells, upregulated modules were associated with cell adhesion and endothelial functions. One downregulated module was associated with immune system-related functions. Querying the STRING database revealed known functional-interaction networks underlying the modules. Several possible hub genes were identified, of which some (for example FEN1, BIRC5, NEK2, CDKN3, and TTK) are potentially druggable as determined by querying the Drug Gene Interaction database. In summary, our study provides a detailed picture of the transcriptomic differences between tumour and non-tumour endothelium in the liver on a co-expression network level, indicates several potential therapeutic targets and presents an analysis workflow that can be easily adapted to other projects.

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IGF2BP2 Promotes Liver Cancer Growth Through an m6A-FEN1-Dependent Mechanism

Cited by 95 publications

References 32 publications

The role of IGF2BP2, an m6A reader gene, in human metabolic diseases and cancers

The role of IGF2BP2, an m6A reader gene, in human metabolic diseases and cancers

IGF2BP2 Promotes the Proliferation, Invasion and Migration of Esophageal Carcinoma Cells via Activation of the PI3K/AKT/EMT Signaling Pathway

Systematic Analysis of the Transcriptome Profiles and Co-Expression Networks of Tumour Endothelial Cells Identifies Several Tumour-Associated Modules and Potential Therapeutic Targets in Hepatocellular Carcinoma

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