Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
, 14 (2), 1523-30

Silencing Cyclin-Dependent Kinase Inhibitor 3 Inhibits the Migration of Breast Cancer Cell Lines

Affiliations

Silencing Cyclin-Dependent Kinase Inhibitor 3 Inhibits the Migration of Breast Cancer Cell Lines

Miao Deng et al. Mol Med Rep.

Abstract

Cyclin-dependent kinase inhibitor 3 (CDKN3) belongs to the dual-specificity protein phosphatase family, which is hypothesized to regulate cell cycle progression in tumor cells. However, whether CDKN3 is a potential therapeutic target for breast cancer remains to be elucidated. The present in vitro study aimed to investigate the potential roles of CDKN3 in breast cancer. Breast cancer cell lines were used to detect CDKN3 expression, and CDKN3 expression was silenced to investigate its role in cell apoptosis, cell cycle arrest and migration. The underlying mechanisms were screened by detecting proliferating cell nuclear antigen (PCNA), Ras homolog gene family, member A (RhoA), vimentin, B‑cell lymphoma 2 (Bcl‑2) and Bcl‑2‑associated X protein (Bax) expression. CDKN3 was highly expressed in MCF‑7 and BT474 cell lines. The silencing of CDKN3 in MCF‑7 and BT474 cell lines promoted cell apoptosis, induced G1 phase cell cycle arrest and inhibited cell migration. The expression levels of PCNA, RhoA, vimentin and Bcl‑2 were downregulated following CDKN3 silencing. Conversely, Bax expression was increased, as compared with the vehicle control. These results suggest that CDKN3 acts as an oncogene during breast cancer progression. The in vitro silencing of CDKN3 promoted apoptosis, induced G1 phase cell cycle arrest and inhibited cell migration. Possible mechanisms are associated with the regulation of PCNA, Bcl‑2, vimentin, RhoA and Bax expression. CDKN3 may therefore be considered a potential target for the treatment of breast cancer.

Figures

Figure 1
Figure 1
(A) CDKN3 was highly expressed in the MCF-7 and BT474 cell lines. siRNA was used to silence CDKN3 expression in (B) MCF-7 and (C) BT474 cells. (D) CDKN3 protein expression levels relative to GAPDH. Data are presented as the mean ± standard deviation. *P<0.05; **P<0.01; ***P<0.001 vs. the control group. CDKN3, cyclin-dependent kinase inhibitor 3; siRNA, small interfering RNA; GAPDH, glyceraldehyde 3-phosphate dehydrogenase.
Figure 2
Figure 2
(A) Cyclin-dependent kinase inhibitor 3 silencing decreased cell migration in MCF-7 and BT474 cells. Magnification, ×10. (B) Migration index was measured. Data are presented as the mean ± standard deviation. **P<0.01; ***P<0.001 compared with the control group. siRNA, small interfering RNA.
Figure 3
Figure 3
(A) Cyclin-dependent kinase inhibitor 3 silencing induced apoptosis in MCF-7 and BT474 cells. (B) Percentage of apoptosis was determined. Data are presented as the mean ± standard deviation. ***P<0.001 compared with the control group. siRNA, small interfering RNA.
Figure 4
Figure 4
(A) Cyclin-dependent kinase inhibitor 3 silencing resulted in a G1-phase cell cycle arrest in MCF-7 and BT474 cells. (B) Number of cells in G1 phase was determined. Data are presented as the mean ± standard deviation. *P<0.05; **P<0.01 compared with the control group. siRNA, small interfering RNA.
Figure 5
Figure 5
(A) Cyclin-dependent kinase inhibitor 3 silencing downregulated PCNA, Bcl-2, vimentin and RhoA expression levels, and upregulated Bax expression levels in (B) MCF-7 and (C) BT474 cells. Data are presented as the mean ± standard deviation. *P<0.05; **P<0.01; ***P<0.001 compared with the control group. PCNA, proliferating cell nuclear antigen; Bcl-2, B-cell lymphoma 2; Bax, Bcl-2-associated X protein; RhoA, Ras homolog gene family, member A; siRNA, small interfering RNA; GAPDH, glyceraldehyde 3-phosphate dehydrogenase.

Similar articles

See all similar articles

Cited by 9 articles

See all "Cited by" articles

References

    1. Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J Clin. 2014;64:9–29. doi: 10.3322/caac.21208. - DOI - PubMed
    1. Baghdassarian N, Ffrench M. Cyclin-dependent kinase inhibitors (CKIs) and hematological malignancies. Hematol Cell Ther. 1996;38:313–323. doi: 10.1007/s00282-996-0313-4. - DOI - PubMed
    1. Malumbres M. Cyclin-dependent kinases. Genome Biol. 2014;15:122. doi: 10.1186/gb4184. - DOI - PMC - PubMed
    1. Berumen J, Espinosa AM, Medina I. Targeting CDKN3 in cervical cancer. Expert Opin Ther Targets. 2014;18:1149–1162. doi: 10.1517/14728222.2014.941808. - DOI - PubMed
    1. García-Escudero R, Martínez-Cruz AB, Santos M, Lorz C, Segrelles C, Garaulet G, Saiz-Ladera C, Costa C, Buitrago-Pérez A, Dueñas M, Paramio JM. Gene expression profiling of mouse p53-deficient epidermal carcinoma defines molecular determinants of human cancer malignancy. Mol Cancer. 2010;9:193. doi: 10.1186/1476-4598-9-193. - DOI - PMC - PubMed

MeSH terms

Substances

Feedback