Abstract
The expression of Centromere Protein U (CENP-U) is closely related to tumor malignancy. Till now, the role of CENP-U in the malignant progression of breast cancer remains unclear. In this study, we found that CENP-U protein was highly expressed in the primary invasive breast cancer tissues compared to the paired adjacent histologically normal tissues and ductal carcinoma in situ (DCIS) tissues. After CENP-U was knocked down, the proliferation and colony-forming abilities of breast cancer cells were significantly suppressed, whereas the portion of apoptotic cells was increased. Meanwhile, the PI3K/AKT/NF-κB pathway was significantly inhibited. In vivo studies showed that, the inhibition of CENP-U repressed the tumor growth in orthotopic breast cancer models. Therefore, our study demonstrated that the CENP-U might act as an oncogene and promote breast cancer progression via activation of the PI3K/AKT/NF-κB pathway, which suggests a promising direction for targeting therapy in breast cancer.
Highlights
Centromeres, the essential chromosomal domains in cell mitosis and meiosis, provide a structural platform for kinetochore assembling to guarantee the correct chromosome segregation [1, 2]
Centromere Protein U (CENP-U) expression in cancer cells was significantly higher than in normal tissues and the number of centromere-associated proteins (CENPs)-U positive cells in IDC were higher than DICS, suggesting that CENP-U expression level was up-regulated with the development of breast cancer
A significantly increased CENP-U expression was found in IDC compared to DICS, which was consistent with previous results [22]
Summary
Centromeres, the essential chromosomal domains in cell mitosis and meiosis, provide a structural platform for kinetochore assembling to guarantee the correct chromosome segregation [1, 2]. The kinetochore, the CENPs assembled at each centromere along with multiple other kinds of proteins that are involved in the microtubule attachment. CENPs can act as the attachment site for spindle microtubules and can serve as the site at which produces force to drive chromosome movement during mitosis [5,6,7]. Centromere protein A (CENP-A) is over-expressed in colorectal cancer cell lines and suggested to be an independent prognostic marker for patients with estrogen receptor (ER)-positive breast cancer who received no systemic therapy [8, 9]. Centromere protein H (CENP-H) has been demonstrated to be a novel biomarker related to the survival in patients with hepatocellular carcinoma [17]
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