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Suppression of CCT3 inhibits melanoma cell proliferation by downregulating CDK1 expression
Wenlou Liu1, Xiuli Zhang2, Cheng Chen3
1Department of Oncology, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, China.
Abstract:
The eukaryotic chaperonin family is vital for cell survival. The dysregulation of chaperonin-containing TCP-1 subunit 3 (CCT3) is implicated in several types of malignant tumors' development. However, its functional role in melanoma remains unknown. Here we elucidate the functional contribution to CCT3 to melanoma progression. The results indicated that CCT3 highly expressed in melanoma tissues, and CCT3 overexpression is correlated with clinical stage in melanoma patients. Knockdown of CCT3 by shRNA in melanoma cells inhibited cell proliferation and cell cycle progression and induced cell apoptosis in vitro. In vivo, tumor growth in the nude mice was significantly inhibited after CCT3 silencing. Importantly, the gene array analysis showed that CCT3 depletions inhibited cyclins and cell cycle regulation signaling and further evaluation demonstrated that CDK1 expression was significantly decreased after CCT3 knockdown. Additionally, Functional rescues experiments also indicated that decreased cell proliferation due to CCT3 silencing was rescued by CDK1 overexpression. Overall, our findings suggest that CCT3 depletions prohibited melanoma progression by downregulating CDK1 expression and is a potential therapeutic target for melanoma.
Insights
Chaperonin-containing TCP-1 subunit 3 (CCT3) promotes melanoma progression by increasing cell proliferation and survival. Silencing CCT3 inhibits tumor growth by downregulating CDK1, suggesting CCT3 as a potential therapeutic target for melanoma.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- The eukaryotic chaperonin family is essential for cellular functions.
- Dysregulation of chaperonin-containing TCP-1 subunit 3 (CCT3) is linked to various cancers.
- The role of CCT3 in melanoma progression is currently unknown.
Purpose of the Study:
- To investigate the functional role of CCT3 in melanoma progression.
- To determine if CCT3 can be a therapeutic target for melanoma.
Main Methods:
- Gene expression analysis of CCT3 in melanoma tissues.
- In vitro studies using shRNA to knockdown CCT3 in melanoma cells.
- In vivo tumor xenograft models in nude mice.
- Gene array analysis to identify downstream signaling pathways.
- Functional rescue experiments with CDK1 overexpression.
Main Results:
- CCT3 was highly expressed in melanoma tissues and correlated with clinical stage.
- CCT3 knockdown inhibited melanoma cell proliferation, cell cycle progression, and induced apoptosis in vitro.
- Tumor growth was significantly inhibited in nude mice after CCT3 silencing.
- CCT3 depletion downregulated cyclins, cell cycle regulators, and specifically decreased CDK1 expression.
- Overexpression of CDK1 rescued the decreased cell proliferation caused by CCT3 silencing.
Conclusions:
- CCT3 promotes melanoma progression by enhancing cell proliferation and survival.
- CCT3 downregulation inhibits melanoma progression, primarily through the downregulation of CDK1.
- CCT3 represents a potential therapeutic target for melanoma treatment.
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