Targeting IGF2BP3 in HNSCC: Identification and Virtual Screening of Inhibitors

Abstract

Background

Resistance to traditional intense chemotherapy and high invasiveness are characteristics of head and neck squamous cell cancer (HNSCC). Numerous human disorders are linked to N6-methyladenosine (m6A) modification of RNA, and the genetic changes in m6A regulatory genes in HNSCC are not well-understood. There is also a pressing need to find efficient targets and inhibitors for the treatment of HNSCC. This investigation examined the RNA m6A alteration in HNSCC and found putative IGFBP3 inhibitors for potential use.

Methods

We examined m6A regulator gene expression data from the public Gene Expression Omnibus (GEO) database in both normal tissues and patient HNSCC. For bioinformatics analysis, the R package and additional tools, including the m6A2Target database, Gene Ontology (GO) functional and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, Gene Expression Profiling Interactive Analysis (GEPIA), and Human Protein Atlas, were used to examine the molecular mechanisms and prognostic impact for regulators that are distinctly expressed. Furthermore, TCMBank molecules were employed for virtual screening to find possible inhibitors.

Results

Out of the 151 differentially expressed genes (DEGs) found in the chosen datasets, insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) was the m6A regulator that was elevated in HNSCC. The GO and KEGG analyses revealed that the target genes of IGF2BP3 were mostly enriched in several pathways and activities linked to cancer. In patients with HNSCC, IGF2BP3 showed an effective predictive effect by GEPIA analysis. Virtual screening yielded four traditional Chinese medicine ingredients as putative IGF2BP3 inhibitors for additional research.

Discussion

This work learned the role and prognostic effect of IGF2BP3 in HNSCC; meanwhile, the potential inhibitors of IGF2BP3 were identified for further study.

Keywords

head and neck squamous cell carcinoma - IGF2BP3 - prognosis - inhibitors - virtual screening

CRediT Authorship Contribution Statement

Guoyi Yan: Conceptualization, writing original draft, funding acquisition, project administration, and writing-review and editing. Ge Liu: Writing original draft. Wei Zhao: Conceptualization, investigation, and methodology. Zhenjiang Qiu: Conceptualization, funding acquisition, and investigation. Mingyuan Wu: Conceptualization, and supervision. Mengyao Luo: Investigation, and methodology. Shuyi Yan: Investigation, and methodology. Yange Xing: Investigation, and methodology. Muhammad Noman Khan: Investigation, and methodology. Shouhu Li: Conceptualization, writing original draft, funding acquisition, and writing-review and editing. Yonghua Qi: Conceptualization, writing original draft, funding acquisition, and writing-review and editing.

Publication History

Received: 28 June 2025

Accepted: 12 August 2025

Article published online:
30 December 2025

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