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RNF130 inhibits the proliferation, migration and invasion of osteosarcoma through DAB1 mediated suppression of the
Wenda Liu1, Liangyu Guo1, Zhengping Liu1
1Department of Orthopaedics, Renmin Hospital of Wuhan University, Hubei Province, Wuhan 430060, China.
Background:
Ring finger protein 130 (RNF130) is also known as Goliath. It is the mammalian homolog of the Drosophila E3 ligase Goliath (dGoliath), which is localized to the protease-associated (PA) domain. Although RNF130 has been investigated in other research areas, its functional role in osteosarcoma remains poorly defined.
Methods:
We initially analyzed the expression of RNF130 in osteosarcoma via an online database and explored its association with patient survival prognosis. Subsequently, the influence of RNF130 on osteosarcoma malignancy was verified using in vivo phenotypic assays. Furthermore, the molecular mechanism underlying RNF130-mediated regulation of osteosarcoma progression was elucidated by transcriptome sequencing and co-immunoprecipitation. Finally, a xenograft tumor model was constructed in nude mice to verify the regulatory effect of RNF130 on osteosarcoma growth in vivo.
Results:
RNF130 expression was significantly decreased in osteosarcoma tissues and was associated with overall survival in the TCGA dataset. Functional assays demonstrated that overexpression of RNF130 inhibits the proliferation, migration, and invasion of osteosarcoma cells. Conversely, silencing of RNF130 promoted these malignant phenotypes. Mechanistic investigations revealed that RNF130 functions as a tumor suppressor in osteosarcoma by regulating the DAB1/PI3K/AKT/mTOR signaling axis via the ubiquitin-proteasome pathway.
Conclusion:
RNF130 may be associated with prognosis in osteosarcoma and suppresses malignant progression by regulating the DAB1/PI3K/AKT/mTOR signaling pathway. Its clinical prognostic value still requires validation in larger independent datasets.
Insights
Ring finger protein 130 (RNF130) acts as a tumor suppressor in osteosarcoma. Its decreased expression correlates with poor prognosis, and it inhibits cancer cell proliferation and metastasis by regulating the DAB1/PI3K/AKT/mTOR pathway.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Ring finger protein 130 (RNF130), also known as Goliath, is the mammalian homolog of Drosophila E3 ligase dGoliath.
- Its precise role in osteosarcoma pathogenesis is not well understood, despite its investigation in other biological contexts.
Purpose of the Study:
- To investigate the expression and functional role of RNF130 in osteosarcoma.
- To elucidate the molecular mechanisms by which RNF130 influences osteosarcoma progression and patient survival.
Main Methods:
- Analysis of RNF130 expression in osteosarcoma using TCGA dataset and correlation with patient survival.
- In vivo phenotypic assays to assess the impact of RNF130 on osteosarcoma malignancy.
- Transcriptome sequencing and co-immunoprecipitation to identify RNF130 regulatory pathways.
- Xenograft tumor models in nude mice to validate RNF130's role in tumor growth.
Main Results:
- RNF130 expression is significantly reduced in osteosarcoma tissues and linked to poorer overall survival.
- Overexpression of RNF130 suppresses osteosarcoma cell proliferation, migration, and invasion, while RNF130 silencing promotes these malignant behaviors.
- RNF130 functions as a tumor suppressor by regulating the DAB1/PI3K/AKT/mTOR signaling pathway through the ubiquitin-proteasome system.
Conclusions:
- RNF130 exhibits tumor-suppressive activity in osteosarcoma, potentially serving as a prognostic biomarker.
- RNF130 regulates osteosarcoma progression via the DAB1/PI3K/AKT/mTOR signaling pathway.
- Further validation in larger, independent datasets is necessary to confirm the clinical prognostic value of RNF130.
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