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Siah1 promotes the proliferation of NSCLC cells through ubiquitinating and stabilizing Notch1

Yan Liu1, Qingling Li1, Liang Geng1

  • 1Department of Respiratory and Critical Care Medicine, Xuzhou No.1 People's Hospital, Xuzhou, Jiangsu, China.

Experimental Cell Research
|August 12, 2022
PubMed

Insights

Seven in absentia homolog 1 (Siah1) promotes non-small cell lung cancer (NSCLC) proliferation by stabilizing Notch1, leading to increased Akt phosphorylation. This study reveals Siah1 as a potential oncogene target in NSCLC treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Seven in absentia homolog 1 (Siah1) is implicated in various cancers.
  • The specific role of Siah1 in non-small cell lung cancer (NSCLC) pathogenesis is not well understood.

Purpose of the Study:

  • To elucidate the function and molecular mechanisms of Siah1 in NSCLC.
  • To investigate the relationship between Siah1, Notch1, and cancer cell proliferation.

Main Methods:

  • Bioinformatic analysis to identify potential Siah1 targets.
  • In vitro experiments involving Siah1 knockdown and overexpression in NSCLC cells.
  • Assessment of protein ubiquitination, stabilization, and phosphorylation (Akt).
  • Correlation analysis with human NSCLC tissue samples.

Main Results:

  • Siah1 knockdown inhibited NSCLC cell proliferation, while Siah1 overexpression promoted it.
  • Notch receptor 1 (Notch1) was identified as a target of Siah1.
  • Siah1 functions as an E3 ligase, promoting Notch1 ubiquitination and stabilization via the proteasome pathway.
  • Siah1 expression positively correlated with CTR9 in NSCLC tissues.
  • Siah1 promotes Akt phosphorylation by regulating Notch1, driving NSCLC cell proliferation.

Conclusions:

  • Siah1 acts as an oncogene in NSCLC.
  • Siah1 stabilizes Notch1 through ubiquitination and the proteasome pathway.
  • The Siah1-Notch1 axis promotes NSCLC cell proliferation via Akt activation, representing a potential therapeutic target.
Keywords:
AktNSCLCNotch1ProliferationSiah1

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