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PLoS One. 2015 Sep 15;10(9):e0137397. doi: 10.1371/journal.pone.0137397. eCollection 2015.

CDKN3 mRNA as a Biomarker for Survival and Therapeutic Target in Cervical Cancer.

Author information

1
Unidad de Medicina Genómica, Facultad de Medicina, Universidad Nacional Autónoma de México/ Hospital General de México, México City, México; Departamento de Medicina Experimental, Facultad de Medicina, Universidad Nacional Autónoma de México, México City, México.
2
Servicio de Oncología, Hospital General de México, México City, México.
3
Departamento de Neuropatología Molecular, División de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, México City, México.
4
Unidad de Medicina Genómica, Facultad de Medicina, Universidad Nacional Autónoma de México/ Hospital General de México, México City, México.
5
Departamento de Inmunología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México City, México; Laboratorio de Biología Molecular, Asociación para Evitar la Ceguera en México Hospital Dr. Luis Sánchez-Bulnes, México City, México.
6
Servicio de Genética, Hospital General de México/Facultad de Medicina, Universidad Nacional Autónoma de México, México City, México.
7
Departamento de Medicina Experimental, Facultad de Medicina, Universidad Nacional Autónoma de México, México City, México.

Abstract

The cyclin-dependent kinase inhibitor 3 (CDKN3) gene, involved in mitosis, is upregulated in cervical cancer (CC). We investigated CDKN3 mRNA as a survival biomarker and potential therapeutic target for CC. CDKN3 mRNA was measured in 134 CC and 25 controls by quantitative PCR. A 5-year survival study was conducted in 121 of these CC patients. Furthermore, CDKN3-specific siRNAs were used to investigate whether CDKN3 is involved in proliferation, migration, and invasion in CC-derived cell lines (SiHa, CaSki, HeLa). CDKN3 mRNA was on average 6.4-fold higher in tumors than in controls (p = 8 x 10-6, Mann-Whitney). A total of 68.2% of CC patients over expressing CDKN3 gene (fold change ≥ 17) died within two years of diagnosis, independent of the clinical stage and HPV type (Hazard Ratio = 5.0, 95% CI: 2.5-10, p = 3.3 x 10-6, Cox proportional-hazards regression). In contrast, only 19.2% of the patients with lower CDKN3 expression died in the same period. In vitro inactivation of CDKN3 decreased cell proliferation on average 67%, although it had no effect on cell migration and invasion. CDKN3 mRNA may be a good survival biomarker and potential therapeutic target in CC.

PMID:
26372210
PMCID:
PMC4570808
DOI:
10.1371/journal.pone.0137397
[Indexed for MEDLINE]
Free PMC Article

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