Pan-cancer Analysis To Investigate The Potential Functions Of IGF2BPs Family In Tumors And The Role Of IGF2BP3 In Glioma

The insulin-like growth factor-2 messenger m RNA-binding proteins 1–3(IGF2BP1–3),which regulate RNA processing at multiple levels,including its localization,translation,and stability.Since N6-methyladenosine(m6A)contributes to several types of cancer progression,it is currently one of the most studied m RNA modifications in eukaryotes.IGF2 BPs act as m6 A readers by recognizing and regulating the m6 A modification of target m RNAs,which is crucial for their oncogenic function.However,knowledge regarding the involvement of IGF2 BPs in tumor immunity and stemness across cancer types is still lacking.In this study,we comprehensively analyzed pan-cancer multiomic data to determine the correlation of IGF2 BPs m RNA and protein expression with various cancer parameters such as mutation frequency,prognostic value,the tumor microenvironment(TME),checkpoint blockade,tumor immune infiltration,stemness and drug sensitivity.Quantitative real-time PCR was used to validate the expression of IGF2 BPs in cancer samples and glioma cells,as well as immunofluorescence staining.By using sphere formation,cytotoxicity,transwell,and wound healing assays,we investigated the functional role of IGF2BP3 in glioma stem cell(GSC).The results showed that IGF2 BPs are expressed at increased levels in most malignant tumors and different cancer cell lines and have low survival rates in a variety of tumors,where we found that IGF2BP1 and 3 are expressed at very low levels in most normal tissues.Importantly,IGF2 BPs can be reexpressed in a wide range of cancer types and in different cancer cell lines,where their expression is usually associated with poor prognosis.Among them,this study found a significant relationship between the expression of IGF2 BPs and the degree of tumor immune infiltration and cancer stemness.The expression of IGF2BP2 and IGF2BP3 in cancer tissues was higher than that in adjacent normal tissues,as shown by immunofluorescence staining and q RT-PCR analysis.In particular,high expression of IGF2 BPs was found to be associated with poor prognosis in glioma patients.The gene knockdown of IGF2BP3 demonstrated that it is involved in maintaining and self-renewing GSCs.In vitro functional assays revealed that knockdown of IGF2BP3 inhibited proliferation,invasion,and migration of GSCs and gliomas.This study systematic pan-cancer study confirmed the identification of IGF2 BPs as therapeutic targets and highlighted the need to study their association with stemness,and the TME,which contribute to the cancer drug-discovery research.Especially,preliminary studies demonstrate the IGF2BP3 as a potential negative regulator of glioma tumorigenesis by modulating stemness.