# The Regulatory Interplay of the Colorectal Cancer Biomarkers MACC1 and IER2 and Its Impact on Metastatic Cancer Survival

## TL;DR

This study explores how two biomarkers, MACC1 and IER2, interact in colorectal cancer and how their combined levels affect patient survival.

## Contribution

The study reveals a functional regulatory relationship between MACC1 and IER2 in colorectal cancer and links their co-expression to patient survival outcomes.

## Key findings

- MACC1 positively regulates IER2 expression and interacts with it at the protein level.
- High levels of both MACC1 and IER2 are associated with shorter survival in colorectal cancer patients.
- MACC1 enhances cell proliferation only when IER2 is overexpressed, not when it is knocked down.

## Abstract

We have previously identified MACC1 and IER2 as functional biomarkers in the context of colorectal cancer. In silico correlation analysis suggested a possible functional connection between the expressions of these biomarkers, given that a significant positive correlation between IER2 and MACC1 RNA was observed. In loss- and gain-of-function experiments, we found that MACC1 positively regulates the expression of IER2. Furthermore, pulldown experiments provided evidence for MACC1-IER2 protein–protein interactions. Functionally, MACC1 enhanced proliferation of HCT116 cells overexpressing IER2 but not of HCT116 cells with knockdown of IER2 expression. Patients with high expressions of both biomarkers lived significantly shorter, whereas those with low concentrations of both markers showed the longest survival. Taken together, these findings show a functional interplay between the colorectal biomarkers MACC1 and IER2, which, in turn, has an impact on the survival of colorectal cancer patients.