Abstract
Breast cancer is a frequent cancer among women. The current study investigated the biological functions of Nek2 in breast cancer and its possible mechanism. The mRNA expression of Nek2 in breast epithelial cells and eight breast cancer cell lines was detected by qRT-PCR. Silencing Nek2 was transfected into MDA-MB-231 and MCF7 cells to examine its roles in the viability, migration, invasion, cell colony, apoptosis and cell cycle of the breast cancer cells by performing CCK-8, wound scratch, Transwell, clone formation and flow cytometry assays, respectively. The expressions of related genes were detected using qRT-PCR and Western blot. MAPK pathway agonist IGF (insulin-like growth factor-1) was added into MDA-MB-231 and MCF7 cells and then cell viability was examined. Nek2 expression was frequently up-regulated in breast cancer cell lines, and silencing Nek2 significantly inhibited the viability, cell migration, invasion and clone formation, promoted cell apoptosis of MDA-MB-231 and MCF7 cells, and arrested cell cycle in G0/G1 phase. Furthermore, knocking down Nek2 decreased the mRNA and protein expressions of Bcl-2, CyclinB1 and CyclinD1, and increased Bax and p27 expressions. Moreover, knocking down Nek2 inhibited the phosphorylation of ERK and p38, and almost completely reversed the expression of p-ERK increased by IGF, but Nek2 knockdown had no obvious effect on p-p38. The inhibitory effect of Nek2 silencing on the cell viability was mainly realized by the inhibition of ERK/MAPK signaling. Nek2 plays an important role in the regulation of the progression of breast cancer in vitro probably through regulating the ERK/MAPK signaling.
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The analyzed data sets generated during the study are available from the corresponding author on reasonable request.
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This work was supported by the Special Research Fund for Central Universities, Peking Union Medical College [Grant No. 3332020026].
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Substantial contributions to conception and design: ZX, MZ. Data acquisition, data analysis and interpretation: XW, JL, GL, KF, XW. Drafting the article or critically revising it for important intellectual content: ZX, MZ. Final approval of the version to be published: All authors. Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of the work are appropriately investigated and resolved: All authors.
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Xing, Z., Zhang, M., Wang, X. et al. Silencing of Nek2 suppresses the proliferation, migration and invasion and induces apoptosis of breast cancer cells by regulating ERK/MAPK signaling. J Mol Histol 52, 809–821 (2021). https://doi.org/10.1007/s10735-021-09979-9
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DOI: https://doi.org/10.1007/s10735-021-09979-9