KEY TAKEAWAYS
- The study aimed to identify a specific pathway by which TRIM8 regulated OC cell proliferation.
- TRIM8 regulated OC proliferation and migration by targeted VDAC2 ubiquitination & degradation.
Ovarian cancer (OC), a prevalent gynecological malignancy with high aggressiveness and unfavorable prognosis, involved TRIM8, yet its specific regulatory role in this cancer remains unclear.
Fei Wu and the team aimed to explore the regulatory mechanism and pathway by which TRIM8 directs OC.
Researchers employed bioinformatics analysis to screen for high expression of TRIM8 in OC, and retrieved the scRNA-seq dataset (5 normal and 7 OC tissue samples) GSE184880 from the GEO database. The expression of TRIM8 was assessed in healthy and OC samples by immunofluorescence.
TRIM8 was silenced or overexpressed in OC cell lines, and the effects on cell proliferation and migration were evaluated using CCK8, transwell, and clonal formation assays, the effect of TRIM8 on OC cells in vivo was assessed through subcutaneous tumor formation experiments in nude mice. The potential interacting protein VDAC2 was identified using mass spectrometry (MS). The mechanism by which TRIM8 potentially regulated VDAC2 was investigated using co-immunoprecipitation and western blotting.
Results unveiled that TRIM8 was found to be overexpressed in OC. In vitro studies demonstrated that TRIM8 enhanced the proliferation and migration of OC cells, while in vivo experiments showed it promoted the growth of subcutaneous tumors in mice. Additionally, 356 patients with OC were selected from the TCGA database and Kaplan–Meier (KM) analyses were performed to evaluate the relationship between the expression of key genes and relapse-free survival (RFS).
Mechanistically, TRIM8 interacted with VDAC2, which led to a decline in the stability of the protein and facilitated its polyubiquitination and subsequent degradation. Knockdown of VDAC2 increased the resistance of OC cells to iron-induced cell death (ferroptosis). Contrastingly, overexpressed VDAC2 mitigated the OC progression induced by TRIM8 overexpression.
The study concluded that TRIM8 directs OC proliferation and migration by targeted ubiquitination and degradation of VDAC2 thus suggesting a novel potential target for OC treatment.
This study was funded by Scientific Research Project of Gusu School of Nanjing Medical University (GSKY20210208 and GSKY20210203), Cultivation Special Project of Gusu School of Nanjing Medical University (GSKY20220522), “Science and Education Revitalize Health” Youth Science and Technology Project of Suzhou (KJXW2020028), Special project of diagnosis and treatment technology for key clinical diseases of Suzhou of Jiangsu Province (LCZX202013), Science and Technology Project of Suzhou of Jiangsu Province (SYS2020175), and Key Research Foundation of Zhenjiang Social Development (SH2022029).
Source: https://pubmed.ncbi.nlm.nih.gov/38881325/
Wu F., Xu J., Jin X., et al. (2024). “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. PMID: 38881325.
