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Published on: May 9, 2020
RNF2 promotes chondrosarcoma progression by regulating ubiquitination and degradation of CBX7
Yue Wu1, Zheng Huang2, Ping Luo3
1Department of Orthopedics, Beijing Chaoyang Hospital, No.8 Gongti South Rd, Chaoyang District, Beijing, 100020, China.
Objective:
Chondrosarcoma (CHS) is resistant to conventional chemotherapy and radiotherapy and currently lacks effective treatment options when in advanced stages. Accordingly, this research investigated the mechanism of RNF2/CBX7 in CHS to drive the development of molecularly targeted drugs for CHS.
Methods:
RNF2 and CBX7 levels were detected in CHS cells and tissues. RNF2 and CBX7 expression was modulated through cell transfection to examine their effects on cell proliferation, apoptosis, migration, and angiogenesis. The correlation between RNF2 and CBX7 levels was determined, and the ubiquitination level of CBX7 was tested. Protein synthesis was blocked in RNF2-knockdown/overexpressing cells with CHX to assess the effect of RNF2 on CBX7 stability. JJ012 cells transfected with LV-sh-RNF2 were subcutaneously injected into nu/nu nude mice to ascertain the action of RNF2 in the growth and metastasis of CHS.
Results:
RNF2 was highly expressed in CHS cells and tissues. RNF2 knockdown curbed CHS cell proliferation, migration, and angiogenesis while promoting apoptosis. RNF2 knockdown in JJ012 cells upregulated CBX7 protein levels and reduced CBX7 ubiquitination, whilst RNF2 had no effect on CBX7 mRNA expression. CBX7 knockdown partially nullified the repressing effects of RNF2 knockdown on CHS cell proliferation, migration, and angiogenesis, and CBX7 overexpression partially abolished the promotional effects of RNF2 overexpression. LV-sh-RNF2 prominently restricted tumor growth and weight and declined lung metastatic nodules and Ki-67-positive cells in mice.
Conclusion:
RNF2 fosters CHS progression by elevating CBX7 degradation via the ubiquitination pathway.
Insights
RNF2 promotes chondrosarcoma (CHS) progression by increasing CBX7 degradation through ubiquitination. Targeting RNF2 may offer new therapeutic strategies for advanced CHS.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Chondrosarcoma (CHS) is a challenging bone cancer with limited treatment options for advanced stages.
- Conventional therapies are often ineffective against CHS, necessitating the development of targeted molecular therapies.
Purpose of the Study:
- To investigate the role of RNF2 and CBX7 in the progression of chondrosarcoma.
- To elucidate the molecular mechanism by which RNF2 influences CHS and to explore its potential as a therapeutic target.
Main Methods:
- RNF2 and CBX7 expression levels were analyzed in CHS cells and tissues.
- In vitro experiments involved modulating RNF2/CBX7 expression to assess effects on cell proliferation, apoptosis, migration, and angiogenesis.
- In vivo studies utilized mouse models to evaluate the impact of RNF2 on tumor growth and metastasis.
Main Results:
- High RNF2 expression was observed in CHS.
- RNF2 knockdown inhibited CHS cell proliferation, migration, and angiogenesis, while promoting apoptosis.
- RNF2 knockdown led to increased CBX7 protein levels and reduced its ubiquitination, indicating RNF2 promotes CBX7 degradation.
- In vivo, RNF2 inhibition significantly restricted tumor growth and metastasis in mice.
Conclusions:
- RNF2 plays a crucial role in promoting chondrosarcoma progression.
- RNF2 facilitates CHS advancement by enhancing CBX7 degradation via the ubiquitination pathway.
- Targeting RNF2 presents a promising strategy for developing novel molecularly targeted therapies for chondrosarcoma.
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