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Down-regulation of SIRT3 promotes ovarian carcinoma metastasis

Xue-Cai Dong1, Li-Min Jing2, Wen-Xiang Wang1

  • 1Department of Genycologic Oncology (Section 1), Xinxiang Central Hospital, Xinxiang, Henan, PR China.

Biochemical and Biophysical Research Communications
|May 25, 2016
PubMed

Insights

Sirtuin-3 (SIRT3) suppresses ovarian cancer (OC) metastasis by down-regulating Twist. Lower SIRT3 levels enhance OC cell migration, invasion, and liver metastasis, revealing a novel SIRT3/Twist axis for therapeutic strategies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Ovarian carcinoma (OC) metastasis remains a primary cause of treatment failure.
  • The role of Sirtuin-3 (SIRT3) in OC metastasis is not well understood.
  • SIRT3, a histone deacetylase, has varied roles depending on cell and tumor types.

Purpose of the Study:

  • To investigate the function and mechanism of SIRT3 in ovarian cancer metastasis.
  • To determine the relationship between SIRT3 expression and OC metastatic potential.
  • To elucidate the molecular pathway involving SIRT3 in OC metastasis.

Main Methods:

  • Analysis of SIRT3 expression in metastatic OC tissues and cell lines.
  • In vitro and in vivo assays to assess the impact of SIRT3 modulation on cancer cell migration, invasion, and metastasis.
  • Investigation of the epithelial-to-mesenchymal transition (EMT) pathway and the role of Twist.
  • Detection of the interaction between SIRT3 and Twist.

Main Results:

  • SIRT3 expression was significantly downregulated in metastatic OC tissues and highly metastatic cell lines.
  • SIRT3 knockdown enhanced OC cell migration, invasion, and liver metastasis.
  • SIRT3 overexpression suppressed OC cell metastatic capabilities.
  • SIRT3 inhibits EMT by down-regulating Twist, with a detected interaction between SIRT3 and Twist.

Conclusions:

  • SIRT3 plays a critical suppressive role in ovarian cancer metastasis.
  • The novel SIRT3/Twist axis regulates OC cell metastasis by inhibiting EMT.
  • This SIRT3/Twist axis represents a potential therapeutic target for treating metastatic OC.
Keywords:
EMTMetastasisOvarian carcinomaSIRT3Twist

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