Abstract

Esophageal squamous-cell carcinoma (ESCC) remains a highly lethal malignancy, with long-term survival still unsatisfactory and an urgent need for clinically relevant molecular targets. Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) is an RNA-binding protein with oncogenic activity in several tumor types, but the signaling events associated with its role in ESCC have not been fully defined. IGF2BP2 expression was examined in paired ESCC and adjacent non-tumor tissues by immunohistochemistry (10 paired samples) and qRT-PCR (16 paired samples). Associations with clinicopathological variables were evaluated in 108 TCGA ESCC cases. Stable lentiviral shRNA-mediated knockdown was established in KYSE30 and ECA109 cells. CCK-8, colony formation, Transwell, EdU, and flow cytometry assays were used to assess proliferation, clonogenic growth, migration, invasion, apoptosis, and cell-cycle distribution. EMT-associated markers were measured by Western blotting and qRT-PCR. RNA sequencing, KEGG enrichment analysis, and rescue experiments using the AKT activator SC79 were performed to explore downstream signaling. IGF2BP2 was upregulated in ESCC tissues at both the transcript and protein levels, and higher expression was associated with unfavorable clinicopathological characteristics. Silencing IGF2BP2 reduced proliferation, colony formation, migration, and invasion, promoted G0/G1 cell-cycle arrest, and increased apoptosis. EMT-associated marker analysis showed decreased Snail and increased Slug expression, indicating that these changes require cautious interpretation. RNA sequencing and KEGG analysis suggested enrichment of PI3K/AKT-related signaling after IGF2BP2 knockdown. IGF2BP2 silencing decreased PI3K and p-PI3K levels, whereas SC79 partly restored migratory and invasive capacities. IGF2BP2 contributes to malignant phenotypes in ESCC and may be associated with PI3K/AKT-related signaling. These findings indicate that IGF2BP2 is a candidate biomarker and poten