COLEC12 regulates apoptosis of osteosarcoma through Toll-like receptor 4-activated inflammation
Guang-Zhang Li1, Jian-Feng Deng1, Ying-Zhao Qi1
1Department of Orthopedics, the First Hospital of Qinhuangdao, Hebei, China.
Objective:
To investigate the role of COLEC12 in osteosarcoma and observe the relationship between COLEC12 knockdown and the inflammation of osteosarcoma. Then, further explore whether the process is regulated by TLR4.
Method:
GEPIA and TCGA systems were used to predict the potential function of COLEC12. Western blot and RT-PCR were used to analyze the protein expression, or mRNA level, of COLEC12 in different tissue or cell lines. The occurrence and development of osteosarcoma were observed by using COLEC12 knockdown lentivirus. The inflammation indexes of osteosarcoma, in vitro and in vivo, were explored. TLR4 knockdown lentivirus was applied to the relationship between COLEC12 and TLR4.
Results:
COLEC12 expression in SARC tumor tissue was higher than in normal, and a high expression of COLEC12 in SARC patients had a worse prognostic outcome. Pairwise gene correlation analysis revealed a potential relationship between COLEC12 and TLR4. The COLEC12 expression and mRNA level in the tumor or Saos-2 cells were increased. COLEC12 knockdown lentivirus could inhibit osteosarcoma development, in vivo and vitro, through reducing tumor volume and weight, weakening tumor proliferation, migration, and invasion, and enhancing apoptosis. Furthermore, COLEC12 knockdown could increase inflammation of osteosarcoma, in vivo and in vitro, through inducing myeloperoxidase (MPO), TLR4, NF-κB, and C3, and expression of related inflammatory factors. Finally, TLR4 knockdown lentivirus inhibits the progress of inflammation after COLEC12 regulation, in vivo and vitro.
Conclusion:
COLEC12 may be able to regulate apoptosis and inflammation of osteosarcoma, and TLR4 may be the downstream target factor of COLEC12 in inflammation.
Insights
This study reveals that COLEC12 promotes osteosarcoma progression and inflammation, potentially via TLR4. Inhibiting COLEC12 or TLR4 offers therapeutic strategies for osteosarcoma treatment.
Area of Science:
- Oncology
- Immunology
Background:
- Osteosarcoma is a primary bone malignancy with poor prognosis.
- The role of COLEC12 in osteosarcoma development and its association with inflammation remain unclear.
Purpose of the Study:
- To investigate the function of COLEC12 in osteosarcoma.
- To explore the relationship between COLEC12, osteosarcoma inflammation, and Toll-like receptor 4 (TLR4).
Main Methods:
- Bioinformatic analysis using GEPIA and TCGA databases.
- Western blot and RT-PCR for gene expression analysis.
- In vitro and in vivo experiments using COLEC12 and TLR4 knockdown lentiviruses.
Main Results:
- COLEC12 expression is upregulated in osteosarcoma tissues and associated with worse patient outcomes.
- COLEC12 knockdown inhibits tumor growth, proliferation, migration, invasion, and enhances apoptosis.
- COLEC12 knockdown exacerbates osteosarcoma inflammation, which is reversed by TLR4 knockdown, suggesting TLR4 as a downstream mediator.
Conclusions:
- COLEC12 plays a significant role in regulating osteosarcoma cell apoptosis and inflammation.
- TLR4 is identified as a potential downstream target of COLEC12 in the context of osteosarcoma inflammation.
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