Role of insulin-like growth factor 2 mRNA binding protein 2 in regulating the progression of triple-negative breast cancer via binding with M6A methylation modified downstream target genes CCL20 and c-MYC.

Abstract

The objective of this study was to investigate the mechanism by which insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) interacts with downstream target genes to influence the progression of triple-negative breast cancer (TNBC). The study involved a total of 80 tissue samples collected from various types of breast cancer tumors and benign breast tumors. The gene expression levels of IGF2BP2 in the samples were quantified using real-time quantitative reverse transcription PCR (qRT-PCR). The abilities of cell proliferation, apoptosis, migration, and invasion in human breast cancer cells (MBA-MD-231), as well as the expression of CCL20 and c-MYC following IGF2BP2 transfection, were measured. The binding of IGF2BP2 to CCL20 and c-MYC mRNA and the methylation levels of CCL20 and c-MYC after IGF2BP2 overexpression were detected using RNA immunoprecipitation-qRT-PCR (RIP-qRT-PCR). As a result, we found: 1) the expression of IGF2BP2 was elevated in all subtypes of breast cancer compared to the benign breast tumor group, with significant differences in the HER-2 overexpression and TNBC groups; 2) IGF2BP2 could promote cell proliferation, invasion, and migration capabilities. Notably, there was no significant difference in apoptosis rate in the experimental group with IGF2BP2 overexpression, while the apoptosis rate significantly increased in the experimental group where IGF2BP2 was silenced. The IGF2BP2 upregulated the expression of CCL20 and c-MYC, directly binding with both, with a significant increase in the methylation levels of CCL20 and c-MYC following IGF2BP2 overexpression. Our results indicate that IGF2BP2 exhibited differential expression across different molecular subtypes of breast cancer, with notable upregulation in triple-negative and HER-2 overexpression breast cancers. IGF2BP2 was found to promote the proliferation, invasion, and migration of TNBC, with no significant effect on apoptosis. By directly binding to CCL20 and c-MYC, it played a role in regulating the progression of TNBC by enhancing the methylation levels of both of these target genes.