# Stabilization of OLFML1 via m6A Reader IGF2BP3 Drives CSC Characteristics Through Hedgehog Pathway Activation in CRC

## TL;DR

This study shows how the IGF2BP3 and OLFML1 proteins work together to promote cancer stemness and tumor growth in colorectal cancer.

## Contribution

The study identifies a novel regulatory mechanism involving IGF2BP3 and OLFML1 in driving cancer stemness through m6A modification and Hedgehog pathway activation.

## Key findings

- High OLFML1 expression promotes CRC cell proliferation and cancer stemness.
- IGF2BP3 stabilizes OLFML1 mRNA via m6A modification and prevents its degradation.
- High co-expression of IGF2BP3 and OLFML1 correlates with larger tumor size and advanced T stage in CRC patients.

## Abstract

Colorectal cancer (CRC) progression is closely associated with cancer stemness, which contributes to poor prognosis and therapeutic resistance. This study identifies OLFML1 as a key target accounting for CRC progression. High expression of OLFML1 promotes CRC cell proliferation and cancer stemness. As for mechanism study, we further revealed that IGF2BP3 as a critical up-stream regulator of OLFML1. Our study indicated that IGF2BP3 stabilizes OLFML1 mRNA through m6A modification, thereby enhancing its expression. In addition, IGF2BP3 prevents OLFML1 degradation via the ubiquitin-proteasome pathway. Clinically, this study demonstrated a positive association between IGF2BP3 and OLFML1 in CRC patient samples. High co-expression of IGF2BP3 and OLFML1 was significantly correlated with larger tumor size and advanced T stage. These findings highlight the IGF2BP3/OLFML1 axis as a potential driver of CRC stemness and Hedgehog pathway activation, offering promising prognostic and therapeutic targets for CRC management.