Key Role of MCUR1 in Malignant Progression of Breast Cancer

Peipei Gao; Ting Peng; Shitong Lin; Wenhua Zhi; Canhui Cao; Ping Wu; Ling Xi; Peng Wu; Qin Yang; Wencheng Ding

doi:10.2147/OTT.S306854

Key Role of MCUR1 in Malignant Progression of Breast Cancer

Onco Targets Ther. 2021 Jul 13:14:4163-4175. doi: 10.2147/OTT.S306854. eCollection 2021.

Authors

Peipei Gao¹, Ting Peng¹, Shitong Lin¹, Wenhua Zhi¹, Canhui Cao¹, Ping Wu¹, Ling Xi^{1

2}, Peng Wu^{1

2}, Qin Yang³, Wencheng Ding^{1

2}

Affiliations

¹ Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.
² Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.
³ Institute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.

Abstract

Background: Mitochondrial calcium uniporter regulator 1 (MCUR1, also known as CCDC90A) is a protein-coding gene that plays a key role in mitochondrial calcium uptake. However, knowledge about its clinical significance in breast cancer is still limited.

Methods: The expression profile of MCUR1 in various cancers was analyzed via the ONCOMINE and Tumor Immune Estimation Resource databases. The correlation between MCUR1 expression and the clinical features of breast cancer was investigated using UALCAN and MEXPRESS. Immunohistochemical analysis was applied to verify the expression of MCUR1 in breast cancer. The prognostic significance of MCUR1 in breast cancer was evaluated using Kaplan-Meier plotter and the PrognoScan database. Gene Set Enrichment Analysis (GSEA) was performed to explore the possible biological functions of MCUR1. In addition, the function of MCUR1 was examined by gene silencing in vitro. Western blotting was applied to detect the expression of proteins.

Results: MCUR1 was overexpressed in breast cancer and significantly related to the clinical characteristics of breast cancer. Results from the public databases and IHC analysis indicated that MCUR1 expression was the highest in triple-negative breast cancer (TNBC). The high expression of MCUR1 was associated with poor overall survival, distant metastasis-free survival, and recurrence-free survival. GSEA showed that the hypoxia pathway, cellular reactive oxygen species (ROS) pathway, epithelial-mesenchymal transition pathway, and notch signaling pathway were differentially enriched in the high MCUR1 expression phenotype. In vitro experiments showed that MCUR1 knockdown in TNBC cell lines led to a decrease in cellular ROS and weakened cell migration and invasion abilities. Moreover, Western blotting showed that MCUR1 knockdown inhibited the epithelial-mesenchymal transition of TNBC cells via the ROS/Nrf2/Notch pathways.

Conclusion: Our study suggests that MCUR1 plays a pivotal role in the malignant progression of breast cancer.

Keywords: MCUR1; breast cancer; epithelial-mesenchymal transition; reactive oxygen species.

Grants and funding

This work was supported by the National Natural Science Foundation of China (82072895 to Peng Wu).