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Updated: Aug 2, 2025

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HRD1 promotes non-small cell lung carcinoma metastasis by blocking autophagy-mediated MIEN1 degradation

Cheng Zeng1, Jing Guo2, Jiajia Wu1

  • 1School of Life Sciences, Chongqing University, Chongqing, P.R. China.

The Journal of Biological Chemistry
|April 19, 2023
PubMed

Insights

HRD1 E3 ubiquitin ligase inhibits autophagy in non-small cell lung cancer (NSCLC) by degrading ATG3. This promotes metastasis by releasing MIEN1, offering new therapeutic targets for lung cancer.

Area of Science:

  • Oncology
  • Cell Biology
  • Molecular Biology

Background:

  • Autophagy dysregulation is linked to cancer development.
  • The role of E3 ubiquitin ligase HRD1 in non-small cell lung carcinoma (NSCLC) metastasis requires further elucidation.

Purpose of the Study:

  • To investigate the novel function of HRD1 in NSCLC metastasis through autophagy regulation.
  • To elucidate the molecular mechanism by which HRD1 influences autophagy and cancer cell behavior.

Main Methods:

  • Investigated HRD1's role in NSCLC metastasis by examining its effect on autophagy.
  • Analyzed HRD1's mechanism involving ATG3 ubiquitination and degradation.
  • Assessed the autophagic degradation of MIEN1 (migration and invasion enhancer 1) in response to HRD1 deficiency.
  • Correlated HRD1 and MIEN1 expression levels in lung tumors.

Main Results:

  • HRD1 inhibits autophagy by promoting ATG3 ubiquitination and subsequent degradation.
  • HRD1 deficiency leads to the autophagic degradation of MIEN1.
  • Both HRD1 and MIEN1 expression are upregulated and positively correlated in lung tumors.
  • A novel mechanism where HRD1-mediated ATG3 degradation inhibits autophagy and promotes MIEN1 release, thus enhancing NSCLC metastasis, was identified.

Conclusions:

  • HRD1 plays a critical role in promoting NSCLC metastasis by inhibiting autophagy via ATG3 degradation.
  • The HRD1-MIEN1 axis represents a novel pathway in lung cancer progression.
  • HRD1 and MIEN1 are potential therapeutic targets for lung cancer treatment.
Keywords:
ATG3HRD1MIEN1NSCLC metastasisautophagy

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