We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Expression and Function Analysis of Mitotic Checkpoint Genes Identifies TTK as a Potential Therapeutic Target for Human Hepatocellular Carcinoma.
- Authors
Liang, Xiao-Dong; Dai, Yue-Chu; Li, Zhao-Yun; Gan, Mei-Fu; Zhang, Shi-Rong; Yin-Pan; Lu, Hong-Sheng; Cao, Xue-Quan; Zheng, Bei-jia; Bao, Ling-Fen; Wang, Dan-Dan; Zhang, Li-Ming; Ma, Sheng-Lin
- Abstract
The mitotic spindle checkpoint (SAC) genes have been considered targets of anticancer therapies. Here, we sought to identify the attractive mitotic spindle checkpoint genes appropriate for human hepatocellular carcinoma (HCC) therapies. Through expression profile analysis of 137 selected mitotic spindle checkpoint genes in the publicly available microarray datasets, we showed that 13 genes were dramatically up-regulated in HCC tissues compared to normal livers and adjacent non-tumor tissues. A role of the 13 genes in proliferation was evaluated by knocking them down via small interfering RNA (siRNA) in HCC cells. As a result, several mitotic spindle checkpoint genes were required for maintaining the proliferation of HCC cells, demonstrated by cell viability assay and soft agar colony formation assay. Then we established sorafenib-resistant sublines of HCC cell lines Huh7 and HepG2. Intriguingly, increased TTK expression was significantly associated with acquired sorafenib-resistance in Huh7, HepG2 cells. More importantly, TTK was observably up-regulated in 46 (86.8%) of 53 HCC specimens. A series of in vitro and in vivo functional experiment assays showed that TTK overexpression promoted cell proliferation, anchor-dependent colony formation and resistance to sorafenib of HCC cells; TTK knockdown restrained cell growth, soft agar colony formation and resistance to sorafenib of HCC cells. Collectively, TTK plays an important role in proliferation and sorafenib resistance and could act as a potential therapeutic target for human hepatocellular carcinoma.
- Subjects
LIVER cancer; CANCER cell culture; ANTINEOPLASTIC agents; TARGETED drug delivery; GENE expression; MICROARRAY technology; CANCER cell proliferation
- Publication
PLoS ONE, 2014, Vol 9, Issue 6, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0097739