Neoplasma Vol.69, No.4, p.940–947, 2022
|
| Title: Silencing of B7-H4 induces intracellular oxidative stress and inhibits cell viability of breast cancer cells via downregulating PRDX3 |
| Author: Hao-Chuan Chen, Min Long, Zhao-Wei Gao, Chong Liu, Xia-Nan Wu, Lan Yang, Ke Dong, Hui-Zhong Zhang |
|
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.
|
|
| Keywords: breast cancer; B7-H4; PRDX3; ROS |
|
|
Published online: 20-Jun-2022
|
| Year: 2022, Volume: 69, Issue: 4 |
Page From: 940, Page To: 947 |
doi:10.4149/neo_2022_220304N241
|
Price:
19.20 €
|
|
|
|
|
|
|
|
