Abstract

NUDIX hydrolase type 5 (NUDT5) is a kind of ADP-ribose pyrophosphatase and nucleotide metabolizing enzyme in cell metabolism. Previous studies have shown NUDT5 expression affected chromosome remodeling, involved in cell adhesion, cancer stem cell maintenance and epithelial to mesenchyme transition in breast cancer cells. Nevertheless, the role of NUDT5 in breast cancer progression and prognosis has not yet been systematically studied. This study explored the association of NUDT5 with the tumor development and poor prognosis in patients with breast cancer. Our results show that the levels of NUDT5 were upregulated in breast cancer cell lines and breast tumor tissues, and the expression of NUDT5 in breast tumor tissues increased significantly when compared with adjacent non-tumorous tissues by immunohistochemical staining of tissue microarrays. Breast cancer patients with high NUDT5 expression had a worse prognosis than those with low expression of NUDT5. In addition, the knockdown of NUDT5 suppressed breast cancer cell lines proliferation, migration and invasion, and dramatically inhibited the AKT phosphorylation at Thr308 and expression of Cyclin D1. The opposite effects were observed in vitro following NUDT5 rescue. Our findings indicated that the high expression of NUDT5 is probably involved in the poor prognosis of breast cancer via the activation of the AKT / Cyclin D pathways, which could be a prognostic factor and potential target in the diagnosis and treatment of breast cancer.

Highlights

  • According to the World Health Organization (WHO), approximately one eighth of women have a lifetime risk of breast cancer [1, 2]

  • AKT phosphorylation at Ser473 is inhibited in T47D cell line but not in MCF7 and MDA-MB-231 cell lines (S1 Fig) Essentially, decreased NUDIX hydrolase type 5 (NUDT5) results in decreased p-AKT(Thr308) and cyclin D1

  • Our data indicated that NUDT5 overexpressed in breast tumors

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Summary

Introduction

According to the World Health Organization (WHO), approximately one eighth of women have a lifetime risk of breast cancer [1, 2]. In United States, breast cancer alone accounts for 30% of all new cancer diagnoses in women in Cancer Statistics 2019 [3]. The high expression of NUDT5 is associated with a poor prognosis of breast cancer. Africa, the incidence of breast cancer is increasing [4,5,6]. Breast cancer is still the most common cause of death in developing countries and its mortality rate is second to lung cancer in developed countries [7]. The pathogenesis of breast cancer is a complex process and remains unclear [8]

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