# Functional and Regulatory Effects of Factor V Leiden and Factor V rs6028 in Breast Cancer

## TL;DR

This study explores how two genetic variants of the coagulation factor V gene may influence breast cancer progression by affecting gene expression and cell death.

## Contribution

The study identifies novel regulatory effects of F5 rs6025 and rs6028 on FV expression and apoptosis in breast cancer cells.

## Key findings

- F5 rs6025 and rs6028 variants increased FV mRNA, protein, coagulant activity, and apoptosis compared to wild type.
- Cis-eQTL analysis showed F5 rs6028 has a regulatory effect on F5 expression.
- Transcription factor binding sites overlap with F5 rs6025, suggesting a regulatory role.

## Abstract

Background/Objectives: Cancer progression and the hemostatic system are closely linked. Coagulation factor V (FV) has a key function in coagulation, with both pro- and anticoagulant functions. FV gene (F5) expression and F5 variants have been linked to breast cancer progression. The direct impact of F5 variants on FV expression and functional effects in breast cancer are unknown. We aimed to investigate whether the F5 variants FV Leiden (F5 rs6025) and F5 rs6028 influenced FV expression, coagulant activity, and apoptosis in breast cancer cells. Methods: MDA-MB-231 cells were transfected with overexpression plasmids containing F5 wild type, F5 rs6025 or F5 rs6028. We investigated the functional impact of the F5 variants on F5 mRNA, FV protein, FV coagulant activity, and apoptosis in vitro, and examined the potential of the variants as transcriptional regulators of F5 expression in silico. Results: Increased F5 mRNA, FV protein, and apoptosis were observed in cells transfected with F5 wild-type overexpression plasmid compared to empty vector. F5 mRNA, protein, coagulant activity, and apoptosis were further increased with the F5 rs6025 and F5 rs6028 variants compared to F5 wild type. Cis-expression quantitative trait loci analyses indicated a regulatory effect of F5 rs6028, and putative transcription factor binding sites for several transcription factors overlapped with the position of F5 rs6025. Conclusions: Our study demonstrated that F5 rs6025 and F5 rs6028 have a regulatory effect on FV synthesis that might affect apoptosis in breast cancer. The F5 variants might therefore enhance the tumor suppressor function of FV in breast cancer.