IGF2BP2 Promotes Liver Cancer Growth Through an M6A-FEN1-Dependent Mechanism

Overview

Journal Front Oncol

Specialty Oncology

Date 2020 Nov 23

PMID 33224879

Citations 70

Authors

Jian Pu

Jianchu Wang

Zebang Qin

Anmin Wang

Ya Zhang

Xianjian Wu

Yi Wu

Wenchuan Li

Zuoming Xu

Yuan Lu

Qianli Tang

Huamei Wei

Affiliations

Soon will be listed here.

Abstract

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in China. N6-methyladenosine (m6A) plays an important role in posttranscriptional gene regulation. METTL3 and IGF2BP2 are key genes in the m6A signal pathway and have recently been shown to play important roles in cancer development and progression. In our work, higher METTL3 and IGF2BP2 expression were found in HCC tissues and were associated with a poor prognosis. In addition, IGF2BP2 overexpression promoted HCC proliferation and . Mechanistically, IGF2BP2 directly recognized and bound to the m6A site on FEN1 mRNA and enhanced FEN1 mRNA stability. Overall, our study revealed that METTL3 and IGF2BP2, acting as an oncogene, maintained FEN1 expression through an m6A-IGF2BP2-dependent mechanism in HCC cells, and indicated a potential biomarker panel for prognostic prediction in liver cancer.

Citing Articles

Multifaceted roles of insulin‑like growth factor 2 mRNA binding protein 2 in human cancer (Review).

Shen J, Ding Y Mol Med Rep. 2025; 31(3).

PMID: 39886962 PMC: 11795254. DOI: 10.3892/mmr.2025.13441.

IGF2BP2 Shapes the Tumor Microenvironment by Regulating Monocyte and Macrophage Recruitment in Bladder Cancer.

Li J, Jiang Y, Ma M, Wang L, Jing M, Yang Z Cancer Med. 2024; 13(24):e70506.

PMID: 39711402 PMC: 11664238. DOI: 10.1002/cam4.70506.

IGF2BP2 promotes lung adenocarcinoma progression by regulating LOX1 and tumor-associated neutrophils.

Qian L, Ji Z, Mei L, Zhao J Immunol Res. 2024; 73(1):16.

PMID: 39688738 DOI: 10.1007/s12026-024-09563-9.

High WTAP expression level as a promising biomarker for poor prognosis in colorectal cancer: a pilot study.

Relucenti M, Tito C, Mercantini P, Pilozzi E, Barbaranelli C, Cristiano L Eur J Histochem. 2024; 68(4).

PMID: 39679554 PMC: 11696005. DOI: 10.4081/ejh.2024.4145.

VIM-AS1, which is regulated by CpG methylation, cooperates with IGF2BP1 to inhibit tumor aggressiveness via EPHA3 degradation in hepatocellular carcinoma.

Han S, Ko J, Jung S, Oh S, Kim D, Kang E Exp Mol Med. 2024; 56(12):2617-2630.

PMID: 39617786 PMC: 11671536. DOI: 10.1038/s12276-024-01352-6.

References

Liu L, Zhou C, Zhou L, Peng L, Li D, Zhang X . Functional FEN1 genetic variants contribute to risk of hepatocellular carcinoma, esophageal cancer, gastric cancer and colorectal cancer. Carcinogenesis. 2011; 33(1):119-23. DOI: 10.1093/carcin/bgr250. View

Yang Y, Hsu P, Chen Y, Yang Y . Dynamic transcriptomic mA decoration: writers, erasers, readers and functions in RNA metabolism. Cell Res. 2018; 28(6):616-624. PMC: 5993786. DOI: 10.1038/s41422-018-0040-8. View

Zaher M, Rashid F, Song B, Joudeh L, Sobhy M, Tehseen M . Missed cleavage opportunities by FEN1 lead to Okazaki fragment maturation via the long-flap pathway. Nucleic Acids Res. 2018; 46(6):2956-2974. PMC: 5888579. DOI: 10.1093/nar/gky082. View

Chen M, Wei L, Law C, Tsang F, Shen J, Cheng C . RNA N6-methyladenosine methyltransferase-like 3 promotes liver cancer progression through YTHDF2-dependent posttranscriptional silencing of SOCS2. Hepatology. 2017; 67(6):2254-2270. DOI: 10.1002/hep.29683. View

Mortezaee K . Human hepatocellular carcinoma: Protection by melatonin. J Cell Physiol. 2018; 233(10):6486-6508. DOI: 10.1002/jcp.26586. View

Deng X, Jiang Q, Liu Z, Chen W . Clinical Significance of an m6A Reader Gene, , in Head and Neck Squamous Cell Carcinoma. Front Mol Biosci. 2020; 7:68. PMC: 7193208. DOI: 10.3389/fmolb.2020.00068. View

Huang H, Weng H, Sun W, Qin X, Shi H, Wu H . Recognition of RNA N-methyladenosine by IGF2BP proteins enhances mRNA stability and translation. Nat Cell Biol. 2018; 20(3):285-295. PMC: 5826585. DOI: 10.1038/s41556-018-0045-z. View

Tong M, Deng Z, Yang M, Xu C, Zhang X, Zhang Q . Transcriptomic but not genomic variability confers phenotype of breast cancer stem cells. Cancer Commun (Lond). 2018; 38(1):56. PMC: 6146522. DOI: 10.1186/s40880-018-0326-8. View

Chen B, Zhang Y, Wang Y, Rao J, Jiang X, Xu Z . Curcumin inhibits proliferation of breast cancer cells through Nrf2-mediated down-regulation of Fen1 expression. J Steroid Biochem Mol Biol. 2014; 143:11-8. DOI: 10.1016/j.jsbmb.2014.01.009. View

10.

Dai D, Wang H, Zhu L, Jin H, Wang X . N6-methyladenosine links RNA metabolism to cancer progression. Cell Death Dis. 2018; 9(2):124. PMC: 5833385. DOI: 10.1038/s41419-017-0129-x. View

11.

Tong J, Flavell R, Li H . RNA mA modification and its function in diseases. Front Med. 2018; 12(4):481-489. DOI: 10.1007/s11684-018-0654-8. View

12.

Tang Z, Li C, Kang B, Gao G, Li C, Zhang Z . GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Acids Res. 2017; 45(W1):W98-W102. PMC: 5570223. DOI: 10.1093/nar/gkx247. View

13.

Hu J, Meng Y, Zhang Z, Yan Q, Jiang X, Lv Z . MARCH5 RNA promotes autophagy, migration, and invasion of ovarian cancer cells. Autophagy. 2016; 13(2):333-344. PMC: 5324849. DOI: 10.1080/15548627.2016.1256520. View

14.

Liu S, Li Q, Chen K, Zhang Q, Li G, Zhuo L . The emerging molecular mechanism of mA modulators in tumorigenesis and cancer progression. Biomed Pharmacother. 2020; 127:110098. DOI: 10.1016/j.biopha.2020.110098. View

15.

Syed Y . Ramucirumab: A Review in Hepatocellular Carcinoma. Drugs. 2020; 80(3):315-322. DOI: 10.1007/s40265-020-01263-6. View

16.

Wang S, Sun C, Li J, Zhang E, Ma Z, Xu W . Roles of RNA methylation by means of N-methyladenosine (mA) in human cancers. Cancer Lett. 2017; 408:112-120. DOI: 10.1016/j.canlet.2017.08.030. View

17.

Chao X, Li L, Wu M, Ma S, Tan X, Zhong S . Comparison of screening strategies for Lynch syndrome in patients with newly diagnosed endometrial cancer: a prospective cohort study in China. Cancer Commun (Lond). 2019; 39(1):42. PMC: 6628486. DOI: 10.1186/s40880-019-0388-2. View

18.

International B . Retracted: Hepatocellular Carcinoma: Novel Molecular Targets in Carcinogenesis for Future Therapies. Biomed Res Int. 2018; 2018:4560161. PMC: 5952504. DOI: 10.1155/2018/4560161. View

19.

Qin L, Tang Z . Recent progress in predictive biomarkers for metastatic recurrence of human hepatocellular carcinoma: a review of the literature. J Cancer Res Clin Oncol. 2004; 130(9):497-513. DOI: 10.1007/s00432-004-0572-9. View

20.

Li Z, Qian P, Shao W, Shi H, He X, Gogol M . Author Correction: Suppression of mA reader Ythdf2 promotes hematopoietic stem cell expansion. Cell Res. 2018; 28(10):1042. PMC: 6170484. DOI: 10.1038/s41422-018-0083-x. View