# Multifaceted role of POU5F1P1 in regulating its parental stem cell gene, POU5F1

## TL;DR

This study explores how the pseudogene OCT4-PG1 regulates the stem cell gene OCT4A in endometrial cancer and stem cells.

## Contribution

The study reveals that OCT4-PG1 functions as a non-coding RNA that suppresses OCT4A translation and enhances its activity through heterodimerization.

## Key findings

- OCT4-PG1 expression inversely correlates with endometrial cancer grade.
- OCT4-PG1's 5′UTR strongly inhibits OCT4A translation.
- OCT4-PG1 enhances OCT4A function via heterodimerization.

## Abstract

The human-specific retrogene POU5F1P1 (OCT4-Pseudogene1; OCT4-PG1), derived from stem cell factor POU5F1 (OCT4A), is predicted to encode an OCT4A-like protein; however, its function remains unclear. This study investigated OCT4-PG1 expression, translational control, and its role in endometrial cancer and stem cell regulation. Quantitative analyses revealed that elevated OCT4A, but not OCT4-PG1, expression correlated with clinical risk factors associated with poor prognosis in patients with endometrial cancer. OCT4-PG1 is under strong translational suppression mediated by its untranslated region and does not function as a protein under normal conditions. Instead, it acts as a non-coding RNA that suppresses OCT4A translation. Structural analyses showed that a single amino acid deletion (Gln259) destabilizes the OCT4-PG1 protein, thereby preventing its tumorigenic and transcriptional functions. Nevertheless, OCT4-PG1 forms heterodimers with OCT4A or SOX2, enhancing the regulatory activity of OCT4A. These findings highlight the regulatory role of pseudogenes in cancer and stem cell biology, with implications for therapies targeting OCT4A-related pathways.

•OCT4-PG1 expression inversely correlates with endometrial cancer grade•OCT4-PG1 5′UTR strongly inhibits OCT4A translation•Single amino acid deletion destabilizes OCT4-PG1 protein•OCT4-PG1 protein enhances OCT4A function via heterodimerization

OCT4-PG1 expression inversely correlates with endometrial cancer grade

OCT4-PG1 5′UTR strongly inhibits OCT4A translation

Single amino acid deletion destabilizes OCT4-PG1 protein

OCT4-PG1 protein enhances OCT4A function via heterodimerization

Biological sciences