Chaperonin containing TCP-1 subunit 3 is critical for gastric cancer growth

Li-Juan Li; Lian-Sheng Zhang; Zhi-Jian Han; Zhi-Yun He; Hao Chen; Yu-Min Li

doi:10.18632/oncotarget.22838

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Research Papers:

Chaperonin containing TCP-1 subunit 3 is critical for gastric cancer growth

Li-Juan Li, Lian-Sheng Zhang, Zhi-Jian Han, Zhi-Yun He, Hao Chen and Yu-Min Li _

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Oncotarget. 2017; 8:111470-111481. https://doi.org/10.18632/oncotarget.22838

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Abstract

Li-Juan Li1,2,*, Lian-Sheng Zhang2,*, Zhi-Jian Han3,*, Zhi-Yun He3, Hao Chen3 and Yu-Min Li3

1School of Life Sciences, Lanzhou University, Lanzhou 730030, P.R. China

2Department of Hematology, Gansu Provincial Key Laboratory of Hematology, Second Hospital of Lanzhou University, Lanzhou 730030, P.R. China

3Department of General Surgery, Gansu Provincial Key Laboratory of Digestive System Tumors, Second Hospital of Lanzhou University, Lanzhou 730030, P.R. China

*These authors have contributed equally to this work

Correspondence to:

Yu-Min Li, email: [email protected]

Hao Chen, email: [email protected]

Keywords: gastric cancer; chaperonin containing TCP-1; CCT3; TRiC

Received: March 17, 2017 Accepted: November 15, 2017 Published: December 01, 2017

ABSTRACT

Background: Members 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.

Methods: The 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.

Results: Higher 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.

Conclusion: Our 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.

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Research Papers:

Chaperonin containing TCP-1 subunit 3 is critical for gastric cancer growth

Abstract