Hepatocellular carcinoma (HCC) or hepatoma is the fifth most common cancer and the third most common cause of cancer-related deaths worldwide. Early detection of HCC still remains challenge. Patients with late-stage HCCs have very limited therapeutic options and relatively poor prognosis. Therefore, recognition of useful tumor marker for the diagnosis of HCC may aid in the management with this lethal malignancy, and designing effective therapies.
In our previous study, through in silico data mining of numerous available cDNA microarray databases, the CDC28 protein kinase regulatory subunit 1B (CKS1B) transcript was found to be frequently upregulated in HCCs and the gene is strongly associated in clinical aggressiveness. Moreover, gain of chromosome 1q copy is one of the most frequently detected alterations in HCC and 1q21 is the most frequent minimal amplifying region. Mammalian CKS1B gene, a member of the highly conserved cyclin kinase subunit 1 protein family, mapped to 1q21.2-q22, which interacts with cyclin-dependent kinases and frequently up-regulated in human HCC specimens, and this gene also has been reported to play oncogenic roles in other human cancers. Furthermore, this gene was identified as an essential cofactor of S-phase kinase-associated protein 2 (SKP2) in the SKP2-containing SKP1-Cullin1-F-box ubiquitin ligase complex¡Vmediated ubiquitination of the cell cycle inhibitor protein cyclin-dependent kinases 1A (p27kip1) that leads to the proteasomal degradation of p27kip1. In the present study, our results indicate that CKS1B overexpression may contribute to hepatocarcinogenesis by enhancing the cellular tumorigenic potential. In addition, CKS1B was correlated with the HCC-derived cells proliferation, and CKS1B knockdown significantly inhibited the tumorigenic potential of HCC-derived cells. In this study, we examined that CKS1B knockdown and overexpressed in HCC cells significantly changed the expression of genes known to participate in various cellular processes, including, apoptosis, cell cycle, proliferation, viability, invasion, and migration, implying that CKS1B may play considerable and diverse roles in hepatocarcinogenesis.
| Identifer | oai:union.ndltd.org:NSYSU/oai:NSYSU:etd-0814112-145819 |
| Date | 14 August 2012 |
| Creators | Ko, Kuan-yu |
| Contributors | Chien-feng Li, Yao-tsung Yeh, Yow-ling Shiue |
| Publisher | NSYSU |
| Source Sets | NSYSU Electronic Thesis and Dissertation Archive |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0814112-145819 |
| Rights | user_define, Copyright information available at source archive |
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