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Published on: May 14, 2016
RNF11 confers chemotherapy sensitivity to tumor cells by regulating the ubiquitination of KU80 and the cell cycle
Cheng Wei1, Xiaojun Li1, Zhen Wei2
1Department of The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou 730000, PR China.
Background:
Ring finger protein 11 (RNF11) is integral to cell signal transduction and transcription factor regulation and is strongly connected to the beginning and progression of malignant tumors. However, the core mechanisms of RNF11 remain unknown to date. This study highlights the significant function of RNF11 in the DNA damage response.
Methods:
After the CRISPR-Cas9 gene knockout of RNF11, HCT116 cells were transfected, and cell viability assays were performed to evaluate the response of tumor cells to the chemotherapy drugs after RNF11 deletion. The interaction of RNF11 with its binding proteins and its ubiquitination mechanism, along with the recruitment of KU80 to chromatin, were subsequently evaluated. RNF11 was revealed to participate in the regulation of the cell cycle and apoptosis. An HCT116 xenograft tumor model was used to validate the in vivo sensitivity of tumors to 5-FU, revealing that RNF11 is essential for regulating the responsiveness of tumor cells to chemotherapy.
Results:
RNF11 modulates KU80 expression and participates in cell cycle regulation. The elimination of RNF11 results in the accumulation of KU80 at the DNA damage sites, induces G1 phase cell cycle arrest, and increases sensitivity to the chemotherapy drugs. Mechanistically, RNF11 regulates KU80 expression through a direct interaction and facilitates its ubiquitination while modulating apoptosis and the cell cycle, thereby participating in the cellular damage response. Furthermore, high RNF11 expression is associated with poor prognosis in patients with cancer, while RNF11 deletion impedes tumor progression and enhances the sensitivity of the xenografts to 5-FU treatment. These findings demonstrate that RNF11 is involved in the clinical tumor treatment processes and could be a target for cancer treatment.
Conclusion:
RNF11 binds with KU80, facilitates its ubiquitination, supports DNA damage repair, preserves genomic stability, and enhances the chemotherapy response in tumor cells.
Insights
Ring finger protein 11 (RNF11) is crucial for DNA damage repair and cell cycle regulation. Its deletion enhances chemotherapy sensitivity and impedes tumor progression, highlighting RNF11 as a potential cancer treatment target.
Area of Science:
- Molecular Biology
- Cancer Research
- Genetics
Background:
- Ring finger protein 11 (RNF11) plays a role in cell signaling and transcription, and is implicated in cancer development and progression.
- The precise mechanisms of RNF11 function, particularly in DNA damage response, remain largely uncharacterized.
- Understanding RNF11's role is critical for developing novel cancer therapies.
Purpose of the Study:
- To elucidate the role of RNF11 in the DNA damage response pathway.
- To investigate the molecular mechanisms by which RNF11 influences cell cycle regulation, apoptosis, and chemotherapy sensitivity.
- To assess the therapeutic potential of targeting RNF11 in cancer treatment.
Main Methods:
- CRISPR-Cas9 gene knockout of RNF11 in HCT116 cells.
- Cell viability assays to assess response to chemotherapy drugs.
- Analysis of RNF11 interactions, ubiquitination, and KU80 recruitment to chromatin.
- In vivo validation using an HCT116 xenograft tumor model treated with 5-fluorouracil (5-FU).
Main Results:
- RNF11 modulates KU80 expression and is involved in cell cycle regulation.
- RNF11 deletion leads to KU80 accumulation at DNA damage sites, G1 cell cycle arrest, and increased sensitivity to chemotherapy.
- RNF11 directly interacts with KU80, facilitating its ubiquitination and influencing apoptosis and cell cycle.
- High RNF11 expression correlates with poor cancer prognosis; RNF11 deletion inhibits tumor progression and enhances xenograft sensitivity to 5-FU.
Conclusions:
- RNF11 binds to KU80, promoting its ubiquitination, thereby supporting DNA damage repair and genomic stability.
- RNF11 negatively regulates the cellular response to DNA damage and chemotherapy.
- RNF11 is a potential therapeutic target for enhancing chemotherapy efficacy in cancer treatment.
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