# Involvement of N4BP2L1, PLEKHA4, and BEGAIN genes in breast cancer and muscle cell development

## TL;DR

This study identifies three genes linked to breast cancer and muscle cell development, suggesting they may act as tumor suppressors.

## Contribution

The study identifies three novel tumor suppressor genes (N4BP2L1, PLEKHA4, BEGAIN) in breast cancer and muscle development.

## Key findings

- N4BP2L1, PLEKHA4, and BEGAIN are downregulated in breast tumors and highly expressed in normal muscle cells.
- Low PLEKHA4 expression correlates with higher breast cancer risk in women who experienced early menopause.
- N4BP2L1 is a potential diagnostic biomarker for breast cancer, particularly in HER2-positive cases.

## Abstract

Patients with breast cancer show altered expression of genes within the pectoralis major skeletal muscle cells of the breast. Through analyses of The Cancer Genome Atlas (TCGA)-breast cancer (BRCA), we identified three previously uncharacterized putative novel tumor suppressor genes expressed in normal muscle cells, whose expression was downregulated in breast tumors. We found that NEDD4 binding protein 2-like 1 (N4BP2L1), pleckstrin homology domain-containing family A member 4 (PLEKHA4), and brain-enriched guanylate kinase-associated protein (BEGAIN) that are normally highly expressed in breast myoepithelial cells and smooth muscle cells were significantly downregulated in breast tumor tissues of a cohort of 50 patients with this cancer. Our data revealed that the low expression of PLEKHA4 in patients with menopause below 50 years correlated with a higher risk of breast cancer. Moreover, we identified N4BP2L1 and BEGAIN as potential biomarkers of HER2-positive breast cancer. Furthermore, low BEGAIN expression in breast cancer patients with blood fat, heart problems, and diabetes correlated with a higher risk of this cancer. In addition, protein and RNA expression analysis of TCGA-BRCA revealed N4BP2L1 as a promising diagnostic protein biomarker in breast cancer. In addition, the in silico data of scRNA-seq showed high expression of these genes in several cell types of normal breast tissue, including breast myoepithelial cells and smooth muscle cells. Thus, our results suggest their possible tumor-suppressive function in breast cancer and muscle development.