Downregulation of Immortalization-Upregulated Protein Suppresses the Progression of Breast Cancer Cell Lines by Regulating Epithelial-Mesenchymal Transition

Cancer Manag Res. 2020 Sep 18:12:8631-8642. doi: 10.2147/CMAR.S259526. eCollection 2020.

Abstract

Introduction: Breast cancer (BC) is one of the most prevalent malignancies in women and its incidence has increased steadily over recent years (0.3% per year). However, the mechanism of BC tumorigenesis remains elaborate elucidation. With the aid of RNA sequencing technology, we discovered that immortalization-upregulated protein (IMUP) is overexpressed in BC tissues compared to normal breast tissues. Our study is to understand the role of IMUP in BC.

Methods: We validated the upregulation of IMUP from multiple public databases. By using quantitative real-time polymerase chain reaction (qRT-PCR), we proved that IMUP is overexpressed in BC tissues and cell lines. We performed proliferation, migration, invasion and apoptosis assays to explore the function of IMUP in BC cell lines (MCF-7 and MDA-MB-231). Besides, we investigated the effect of IMUP silencing on epithelial-mesenchymal transition using Western blotting and qRT-PCR.

Results and discussion: We validated that IMUP expression in BC tissues and cell lines is higher than that in the normal control group. The clinical analysis showed that IMUP is associated with lymph node metastasis and the outcome of neoadjuvant taxol-based therapy. The loss of function assay demonstrated that, with silencing IMUP, the capacities of proliferation, migration, and invasion of BC cell lines were impaired, while the apoptosis rate of cells increased. Meanwhile, the downregulation of IMUP could hinder the procession of epithelial-mesenchymal transition.

Conclusion: Our study proved that IMUP plays a vital role in BC and acts as a potential target and marker in future therapy.

Keywords: BC; EMT; IMUP; breast cancer; epithelial–mesenchymal transition; immortalization-upregulated protein; progression.

Grants and funding

This work was supported by the Natural Science Foundation of Zhejiang Province (LY18H160053, LY17H160053).