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.

Journal of Cancer
|April 11, 2022
PubMed

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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