Multi-omics analysis of N6-methyladenosine reader IGF2BP3 as a promising biomarker in pan-cancer

Abstract

BackgroundInsulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) has been reported to exhibit an oncogenic effect as an RNA-binding protein (RBP) by promoting tumor cell proliferation, migration and invasion in several tumor types. However, a pan-cancer analysis of IGF2BP3 is not currently available, and the exact roles of IGF2BP3 in prognosis and immunology in cancer patients remain enigmatic. The main aim of this study was to provide visualization of the systemic prognostic landscape of IGF2BP3 in pan-cancer and to uncover the potential relationship between IGF2BP3 expression in the tumor microenvironment and immune infiltration profile.MethodsRaw data on IGF2BP3 expression were obtained from GTEx, CCLE, TCGA, and HPA data portals. We have investigated the expression patterns, diagnostic and prognostic significance, mutation landscapes, functional analysis, and functional states of IGF2BP3 utilizing multiple databases, including HPA, TISIDB, cBioPortal, GeneMANIA, GESA, and CancerSEA. Moreover, the relationship of IGF2BP3 expression with immune infiltrates, TMB, MSI and immune-related genes was evaluated in pan-cancer. IGF2BP3 with drug sensitivity analysis was performed from the CellMiner database. Furthermore, the expression of IGF2BP3 in different grades of glioma was detected by immunohistochemical staining and western blot.ResultsWe found that IGF2BP3 was ubiquitously highly expressed in pan-cancer and significantly correlated with diagnosis, prognosis, TMB, MSI, and drug sensitivity in various types of cancer. Besides, IGF2BP3 was involved in many cancer pathways and varied in different immune and molecular subtypes of cancers. Additionally, IGF2BP3 is critically associated with genetic markers of immunomodulators in various cancers. Finally, we validated that IGF2BP3 protein expression was significantly higher in glioma than in normal tissue, especially in GBM.ConclusionsIGF2BP3 may be a potential molecular biomarker for diagnosis and prognosis in pan-cancer, especially for glioma. It could become a novel therapeutic target for various cancers.

FASTKD1 as a diagnostic and prognostic biomarker for STAD: Insights into m6A modification and immune infiltration

“…m6A modification is a common and reversible RNA modification that has an important role in post-transcriptional gene regulation. In recent years, extensive research has been conducted to understand the functional significance of m6A modification and its impact on various biological processes (61)(62)(63). In the present study, a significant correlation was observed between the expression levels of FASTKD1 and two genes, namely YTHDF1 and LRPPRC.…”

Budding yeast as an ideal model for elucidating the role of N6‐methyladenosine in regulating gene expression

“…The fate of m6A‐modified mRNA is determined through proteins that specifically associate with the m6A modification, also known as m6A reader proteins. The first identified and most well studied m6A readers are YTH domain‐containing family of proteins (Chen et al, 2023; Patil et al, 2018; Shao et al, 2021). Over the years YTH domain‐containing proteins have been assigned molecular functions in controlling decay and/or translation of m6A‐modified transcripts.…”

N6-Methyladenosine (m6A) Modification in Natural Immune Cell-Mediated Inflammatory Diseases

“…IGF2BP1/2/3 is non-canonical readers, for which RNA binding depends not only on m6A modification domain but also on other RNA domains. Readers regulate RNA stability, translation, degradation, and splicing [3, 4].…”