CDKN3 mRNA as a Biomarker for Survival and Therapeutic Target in Cervical Cancer
| Autor: | Susana Kofman, Rubén Zamora, Jaime Berumen, Ana Laura Sanchez-Sandoval, E. Martha Pérez-Armendariz, Eligia Juárez, Carlos García-Ruiz, Juan Carlos Gomora, Ana Alfaro, Edgar Román-Bassaure, Ana María Espinosa, Eira Valeria Barrón, Ingrid Medina, Mariano Guardado-Estrada, Miriam Bermúdez |
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| Rok vydání: | 2015 |
| Předmět: |
Carcinogenesis
Down-Regulation Uterine Cervical Neoplasms lcsh:Medicine Biology medicine.disease_cause HeLa Cell Movement Gene expression Biomarkers Tumor medicine Humans Neoplasm Invasiveness Molecular Targeted Therapy RNA Messenger RNA Small Interfering lcsh:Science Papillomaviridae Survival analysis Cell Proliferation Cyclin-Dependent Kinase Inhibitor Proteins Neoplasm Staging Multidisciplinary Base Sequence Cell growth lcsh:R Middle Aged biology.organism_classification Survival Analysis Molecular biology Fold change Gene Expression Regulation Neoplastic Real-time polymerase chain reaction Cancer research Dual-Specificity Phosphatases Biomarker (medicine) Female lcsh:Q Research Article HeLa Cells |
| Zdroj: | PLoS ONE, Vol 10, Iss 9, p e0137397 (2015) PLoS ONE |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0137397 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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