# The Study of Chromobox Protein Homolog 4 in 3D Organoid Models of Colon Cancer as a Potential Predictive Marker

## TL;DR

This study explores the role of CBX4 in colon cancer, showing it promotes tumor growth and could be a new target for treatment and early detection.

## Contribution

The study identifies CBX4 as a novel oncogenic driver and potential biomarker in colorectal cancer.

## Key findings

- CBX4 overexpression increases colorectal cancer cell proliferation, while its silencing reduces tumor growth.
- Pharmacological inhibition of CBX4 in tumor organoids decreases proliferation and alters NF-κB signaling.
- CBX4 inhibition reduces mRNA levels of NF-κB-related genes like TNF, IL-1, and c-Myc.

## Abstract

The Chromobox (CBX) family comprises key epigenetic regulators involved in transcriptional repression through chromatin modifications. Dysregulation of polycomb CBX proteins has been linked to epigenetic gene silencing and cancer progression. However, the specific roles and prognostic value of CBX family members in colorectal cancer (CC) remain unclear. In this study, we show that CBX genes are significantly dysregulated in CC tissues and cell models compared to normal colorectal tissue. Among them, CBX4 and CBX8 emerged as the most upregulated isoforms in tumors. Functional analyses revealed that CBX4 overexpression enhances CC cell proliferation, while its silencing reduces tumor growth. Similarly, pharmacological inhibition of CBX4 in patient-derived tumor organoids led to decreased proliferation, supporting its pro-tumorigenic role. Immunofluorescence analysis further revealed alterations in NF-κB signaling upon CBX4 inhibition, along with reduced mRNA levels of pathway components including NF-κB, TNF, IL-1, and c-Myc. These findings point to a potential interplay between CBX4 and inflammation-related pathways in CC. Overall, our study highlights the oncogenic role of CBX4 in colorectal cancer and supports its potential as a novel therapeutic target and early biomarker for disease progression.