2. Academic Validation
  3. TRIM8 promotes ovarian cancer proliferation and migration by targeting VDAC2 for ubiquitination and degradation

TRIM8 promotes ovarian cancer proliferation and migration by targeting VDAC2 for ubiquitination and degradation

  • Cancer Med. 2024 Jun;13(11):e7396. doi: 10.1002/cam4.7396.
Fei Wu 1,  Jiaqi Xu 1,  Xin Jin 1,  Yue Zhu 2,  Wenxin Gao 3,  Meng Liu 1,  Yan Zhang 1,  Weifeng Qian 2,  Xiaoyan Huang 3,  Dan Zhao 4 5,  Guannan Feng 1,  Shunyu Hou 1,  Xiaoxue Xi 1
Affiliations

Affiliations

  • 1 Department of Obstetrics and Gynecology, The Affiliated Suzhou Hospital of Nanjing Medical University, Gusu School, Nanjing Medical University, Suzhou Municipal Hospital, Suzhou, Jiangsu, China.
  • 2 Department of Breast and Thyroid Surgery, The Affiliated Suzhou Hospital of Nanjing Medical University, Gusu School, Nanjing Medical University, Suzhou Municipal Hospital, Suzhou, Jiangsu, China.
  • 3 Department of Histology and Embryology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, China.
  • 4 Reproductive Medicine Center, The Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, China.
  • 5 Institute of Reproductive Sciences, Jiangsu University, Zhenjiang, China.
PMID: 38881325 DOI: 10.1002/cam4.7396
Abstract

Background: Ovarian Cancer is a common gynecological tumor with high malignant potential and poor prognosis. TRIM8, is involved in the development of various tumors, but its precise regulatory role in ovarian Cancer is still unknown.

Aims: The aim of this study was to explore the specific mechanism by which TRIM8 regulates ovarian Cancer.

Materials and methods: We used bioinformatics analysis to screen for high expression of TRIM8 in ovarian Cancer. The expression of TRIM8 in healthy and cancerous ovarian tissues was assessed by immunofluorescence. TRIM8 was silenced or overexpressed in ovarian Cancer cell lines, with cell proliferation and migration evaluated by CCK8, transwell and clonal formation assays. The effect of TRIM8 on ovarian Cancer cells in vivo was assessed by subcutaneous tumor formation experiments in nude mice. The potential interacting protein VDAC2 was identified by mass spectrometry. The mechanism underlying TRIM8 regulation of VDAC2 was evaluated by co-immunoprecipitation and western blotting.

Results: TRIM8 was overexpressed in ovarian Cancer. TRIM8 promoted the proliferation and migration of ovarian Cancer cells in vitro and the growth of subcutaneous tumors in mice in vivo. TRIM8 interacted with VDAC2, weakened the stability of the protein, and promoted its polyubiquitination and subsequent degradation. Knockdown of VDAC2 increased the resistance of ovarian Cancer cells to iron death, whereas overexpression of VDAC2 attenuated ovarian Cancer progression induced by TRIM8 overexpression.

Discussion: TRIM8 promotes ovarian Cancer proliferation and migration by targeting VDAC2 for ubiquitination and degradation, these finding may provide new targets for the treatment of ovarian Cancer.

Conclusion: TRIM8 degraded VDAC2 through the ubiquitination pathway, increased the resistance of ovarian Cancer cells to iron death, and promoted the proliferation and migration of ovarian Cancer.

Keywords

E3 ubiquitin ligase; TRIM8; VDAC2; ovarian cancer.

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