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Silencing of CDCA5 inhibits cancer progression and serves as a prognostic biomarker for hepatocellular carcinoma.
- Source :
-
Oncology reports [Oncol Rep] 2018 Oct; Vol. 40 (4), pp. 1875-1884. Date of Electronic Publication: 2018 Jul 17. - Publication Year :
- 2018
-
Abstract
- Cell division cycle associated 5 (CDCA5) has been associated with the progression of several types of cancers. However, its possible role and mechanism in hepatocellular carcinoma (HCC) remain unknown. In the present study, immunohistochemical staining and real‑time PCR were used to assess CDCA5 protein and mRNA levels in clinical samples. Statistical analysis was performed to explore the clinical correlation between CDCA5 protein expression and clinicopathological features and overall survival in HCC patients. Cell counting and colony formation assays were employed to analyse the effect of CDCA5 on cell proliferation, and flow cytometry was used to study the role of CDCA5 in cell cycle progression and apoptosis. Moreover, subcutaneous xenograft tumour models were implemented to predict the efficacy of targeting CDCA5 in HCC in vivo. We found that CDCA5 expression was significantly higher in HCC tumour tissues, was associated with clinicopathological characteristics, and predicted poor overall survival in HCC patients. Silencing of CDCA5 with small interfering RNA (siRNA) inhibited cell proliferation and induced G2/M cell cycle arrest in vitro. The xenograft growth assay revealed that CDCA5 downregulation impeded HCC growth in vivo. Further study indicated that CDCA5 depletion decreased the levels of ERK1/2 and AKT phosphorylation in vitro and in vivo. Taken together, these results indicate that CDCA5 may act as a novel prognostic biomarker and therapeutic target for HCC.
- Subjects :
- Adaptor Proteins, Signal Transducing genetics
Animals
Apoptosis
Biomarkers, Tumor genetics
Carcinoma, Hepatocellular genetics
Carcinoma, Hepatocellular metabolism
Case-Control Studies
Cell Cycle
Cell Cycle Proteins genetics
Cell Movement
Cell Proliferation
Female
Follow-Up Studies
Gene Expression Regulation, Neoplastic
Humans
Liver Neoplasms genetics
Liver Neoplasms metabolism
Male
Mice
Mice, Inbred BALB C
Mice, Nude
Middle Aged
Mitogen-Activated Protein Kinase 1 genetics
Mitogen-Activated Protein Kinase 3 genetics
Neoplasm Invasiveness
Prognosis
Proto-Oncogene Proteins c-akt genetics
Signal Transduction
Survival Rate
Tumor Cells, Cultured
Xenograft Model Antitumor Assays
Adaptor Proteins, Signal Transducing metabolism
Biomarkers, Tumor metabolism
Carcinoma, Hepatocellular pathology
Cell Cycle Proteins metabolism
Liver Neoplasms pathology
Mitogen-Activated Protein Kinase 1 metabolism
Mitogen-Activated Protein Kinase 3 metabolism
Proto-Oncogene Proteins c-akt metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1791-2431
- Volume :
- 40
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Oncology reports
- Publication Type :
- Academic Journal
- Accession number :
- 30015982
- Full Text :
- https://doi.org/10.3892/or.2018.6579