Abstract
BackgroundMembers of eukaryotic chaperonin family are essential for cell survival. Dysregulation of Chaperonin containing TCP-1 subunit 3 (CCT3) has been implicated in the development of several types of cancers. However, the role of CCT3 in the development of gastric cancer has yet to be determined.MethodsThe expression patterns of CCT3 in the surgical specimens from 26 gastric cancer patients were evaluated using immunohistochemistry methods. To study the possible roles of CCT3 in the growth and survival of gastric cancer cells, RNA interference was used to knockdown CCT3 expression in gastric cancer cell lines BGC-823 and MGC-803. The effects of CCT3 knockdown on cancer cell proliferation, apoptosis and in vivo growth were examined. Finally, gene expression changes related to CCT3 knockdown were studied using gene array analysis and western blotting.ResultsHigher level of CCT3 expression was detected in the gastric cancer tissue compared to adjacent non-cancerous epithelium. Knockdown of CCT3 inhibited proliferation and colony formation while promoted apoptosis of gastric cancer cells in vitro. Gastric cancer cells exhibited lower growth potential in nude mice when CCT3 expression was suppressed. Gene expression analysis showed that CCT3 knockdown was associated with down-regulation of mitogen-activated protein kinase kinase kinase 7, cell division cycle 42, cyclin D3 and up-regulation of cyclin-dependent kinase 2 and 6.ConclusionOur results suggested that CCT3 played a critical role in gastric cancer growth and survival. Further studies on the mechanisms of CCT3 function is mandated to develop novel cancer treatment targeting CCT3.
Highlights
Gastric cancer is the fourth most common malignancy worldwide and the second most common and lethal cancer in China
Our results suggested that containing TCP-1 subunit 3 (CCT3) played a critical role in gastric cancer growth and survival
CCT3 was upregulated in gastric cancer tissue
Summary
The molecular chaperone network (including chaperons and chaperonins) plays a central role in maintaining protein homeostasis (proteostasis) and proteome integrity. The primary functions of molecular chaperones rely on their ability to transiently bind to hydrophobic regions of nascent or stress-denatured polypeptides and prevent misfolding or aggregation of the proteins. In addition to their pivotal role in ensuring proper folding of polypeptides, molecular chaperones play active role in protein degradation by maintaining target proteins in unfolded state [3]. Members of molecular chaperone pathway have been implicated in the development of cancers [7,8,9]. The role of CCT3 in the development of gastric cancer has yet to be determined
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
