Abstract
BackgroundCytidine nucleotide triphosphate synthase 1 (CTPS1) is a CTP synthase which play critical roles in DNA synthesis. However, its biological regulation and mechanism in triple-negative breast cancer (TNBC) has not been reported yet.MethodsThe expression of CTPS1 in TNBC tissues was determined by GEO, TCGA databases and immunohistochemistry (IHC). The effect of CTPS1 on TNBC cell proliferation, migration, invasion, apoptosis and tumorigenesis were explored in vivo and in vitro. In addition, the transcription factor Y-box binding protein 1 (YBX1) was identified by bioinformatics methods, dual luciferase reporter and chromatin immunoprecipitation (CHIP) assays. Pearson correlation analysis was utilized to assess the association between YBX1 and CTPS1 expression.ResultsCTPS1 expression was significantly upregulated in TNBC tissues and cell lines. Higher CTPS1 expression was correlated with a poorer disease-free survival (DFS) and overall survival (OS) in TNBC patients. Silencing of CTPS1 dramatically inhibited the proliferation, migration, invasion ability and induced apoptosis of MDA-MB-231 and HCC1937 cells. Xenograft tumor model also indicated that CTPS1 knockdown remarkably reduced tumor growth in mice. Mechanically, YBX1 could bind to the promoter of CTPS1 to promote its transcription. Furthermore, the expression of YBX1 was positively correlated with CTPS1 in TNBC tissues. Rescue experiments confirmed that the enhanced cell proliferation and invasion ability induced by YBX1 overexpression could be reversed by CTPS1 knockdown.ConclusionOur data demonstrate that YBX1/CTPS1 axis plays an important role in the progression of TNBC. CTPS1 might be a promising prognosis biomarker and potential therapeutic target for patients with triple-negative breast cancer.
Highlights
Breast cancer (BC) is the most frequently diagnosed malignancy and the leading cause of death from cancer in women worldwide [1]
Cytidine nucleotide triphosphate synthase 1 (CTPS1) is highly expressed in Triple-negative breast cancer (TNBC) tissue and predicts poor prognosis In this study, we firstly explored the CTPS1 expression levels in breast cancer tumor tissues and normal breast tissues in online databases
The results indicated that CTPS1 was highly expressed in TNBC tumor tissues than other breast cancer subtypes or normal breast tissues in all three GEO datasets
Summary
Breast cancer (BC) is the most frequently diagnosed malignancy and the leading cause of death from cancer in women worldwide [1]. Triple-negative breast cancer (TNBC) represents the most aggressive subtype of breast cancer characterized by the absence of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor 2 (HER2). Lin et al Journal of Translational Medicine (2022) 20:17 for about 15–20% of all breast cancer patients, it has the worst outcome due to high invasiveness and unsatisfactory therapeutic efficacy [2, 3]. The use of surgical resection and adjuvant/neoadjuvant chemotherapy is the main treatment strategy for triple-negative breast cancer [2, 4]. Its biological regulation and mechanism in triple-negative breast cancer (TNBC) has not been reported yet
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