Silencing of B7-H4 induces intracellular oxidative stress and inhibits cell viability of breast cancer cells via downregulating PRDX3.

Abstract

Breast cancer (BC) is the most common malignancy in women worldwide, accounting for 15.5% of total cancer deaths. B7-H4 belongs to the B7 family members and plays an important role in the development of a variety of cancers, while Peroxiredoxin III (PRDX3) is an antioxidant protein found in mitochondria. Aberrant expression of B7-H4 or PRDX3 has been implicated in the tumorigenesis of various cancers. However, the functional roles of B7-H4 and PRDX3 in BC and the underlying mechanisms remain unclear. In this research, we found that silencing of B7-H4 by siRNA could lead to not only cell viability inhibition but also the downregulation of PRDX3 in MCF-7 and T47D cells. In order to reveal the roles of PRDX3 in the B7-H4 pathway, we firstly transfected siRNA specifically targeting PRDX3 into MCF-7 and T47D cells, and the results showed that silencing of PRDX3 also inhibited the viability of MCF-7 and T47D cells significantly, accompanied by the increase of reactive oxygen species (ROS) levels. Then we overexpressed the expression of PRDX3 by transfecting PRDX3 expression plasmids into B7-H4 knocking-down cells of MCF-7 and T47D. The results showed that compared with the control groups (MCF-7 or T47D/siNC+pcDNA3.1 vector), cell viabilities were significantly inhibited in RNAi groups (MCF-7 or T47D/siB7-H4+pcDNA3.1 vector), and mildly inhibited in revertant groups (MCF-7 or T47D/siB7-H4+pcDNA3.1 PRDX3), meanwhile, ROS levels significantly elevated in RNAi groups and had no significant changes in revertant groups. All these results indicate that silencing of B7-H4 increases intracellular ROS levels and affects cell viability by modulating the expression of PRDX3 in BC cells, which may provide a potential strategy and therapeutic target for the treatment of BC.

• Authors: Hao-Chuan Chen, Min Long, Zhao-Wei Gao, Chong Liu, Xia-Nan Wu, Lan Yang, Ke Dong, Hui-Zhong Zhang
• Journal: Neoplasma (Neoplasma) Vol. 69 Issue 4 Pg. 940-947 (Jul 2022) ISSN: 0028-2685 [Print] Slovakia
• PMID: 35723197 (Publication Type: Journal Article)

Chemical References

• RNA, Small Interfering
• Reactive Oxygen Species
• V-Set Domain-Containing T-Cell Activation Inhibitor 1
• VTCN1 protein, human
• PRDX3 protein, human
• Peroxiredoxin III

Topics

• Breast Neoplasms (genetics, pathology)
• Cell Survival (genetics)
• Female
• Humans
• Oxidative Stress
• Peroxiredoxin III (genetics, metabolism)
• RNA, Small Interfering (genetics)
• Reactive Oxygen Species
• V-Set Domain-Containing T-Cell Activation Inhibitor 1 (genetics, metabolism)