M6A-Binding Protein IGF2BP2 Promotesproliferation And Metastasis In Papillary Thyroid Carcinoma

Objectives: In recent years,the incidence of thyroid cancer has increased significantly,mainly papillary thyroid cancer(PTC)is the most common.The main reasons for its rapid growth are attributed to the improvement of the level of diagnosis and the popularization of health monitoring.The rapid increase of the incidence of papillary thyroid cancer is accompanied by a stable low mortality rate.Currently,the diagnosis and treatment of papillary thyroid cancer mainly relies on imaging examinations and surgical treatment.The current focus of thyroid cancer research is to balance the relationship between health monitoring,diagnosis and treatment,and to improve the existing thyroid cancer diagnosis and treatment system.To this end,the researchers focused on the molecular mechanisms of thyroid cancer,such as BRAFV600 E mutation and RAS mutation.N6-methyladenosine(m6A)modification is one of the most common RNA modifications,which relies on the synergy of different regulatory factors to play a role including methyltransferases,demethylases and m6A-binding proteins.m6 A modification has been proven to play an important role in the occurrence and development of various tumors,however,the role in thyroid cancer is still unclear.Therefore,this study aimed to explore the role of m6 A modification in thyroid cancer,especially PTC,screen out the m6 A regulators that play an important role in papillary thyroid cancer,and studied its mechanism of action,providing a new direction for the molecular mechanism of papillary thyroid cancer.Method: 1.Using bioinformatics methods to analyze the thyroid cancer data set in the TCGA database,the differential expression of m6 A regulatory factors was obtained from 53 normal thyroid tissues and 419 papillary thyroid cancer tissues.Kaplan-Meier survival analysis and univariate Cox regression analysis were performed on the differentially expressed m6 A regulators,screening out the m6 A regulators with statistical significance.2.Exploring the role of m6A-binding protein IGF2BP2 in papillary thyroid cancer cells.Through overexpression and knockdown of the target gene,the effect of IGF2BP2 on the proliferation and migration of papillary thyroid cancer cells was studied by cell function experiments.3.Exploring the mechanism of IGF2BP2 by RNA-seq and Me-RIP-seq,find its target genes and regulated signaling pathways,and use MeRIP,western blot,and rescue experiments to verify the regulatory pathway.Results: 1.m6 A modification regulators were generally abnormally expressed in papillary thyroid cancer tissues.2.The expression of m6A-binding protein IGF2BP2 was increased in papillary thyroid cancer tissue and affected the prognosis of papillary thyroid cancer.3.The expression of IGF2BP2 was increased in papillary thyroid cancer cells,which promoted the proliferation and migration of papillary thyroid cancer cells.4.Knockdown of IGF2BP2 inhibited the proliferation of papillary thyroid carcinomas in vivo.5.Enrichment analysis of RNA sequencing and Me-RIP sequencing results showed that IGF2BP2 affects NF-κB signaling pathway.6.Me-RIP and other experiments proved that CYLD is the m6 A binding target gene of IGF2BP2,and IGF2BP2 promotes the expression of CYLD,activates the NF-κB signaling pathway,and plays a role in promoting cancer.Conclusions: The m6 A binding protein IGF2BP2 is highly expressed in papillary thyroid cancer,and by recognizing and binding the m6 A binding site on CYLD m RNA,it increases the stability of CYLD m RNA,promotes the expression of CYLD,activates the NF-κB signaling pathway,and promote the proliferation and migration of papillary thyroid cancer cells,and play a cancer-promoting role in papillary thyroid cancer.