COLEC12 regulates apoptosis of osteosarcoma through Toll‐like receptor 4–activated inflammation

• Published in: Journal of clinical laboratory analysis 2020-11, Vol.34 (11), p.e23469-n/a
• Main Authors: Li, Guang‐Zhang, Deng, Jian‐Feng, Qi, Ying‐Zhao, Liu, Ran, Liu, Zhi‐Xin
• Format: Article
• Language: English
• Subjects: Animals; Antibodies; Apoptosis; Apoptosis - genetics; Bone cancer; Cell cycle; Cell Line, Tumor; COLEC12; Collectins - genetics; Collectins - metabolism; Correlation analysis; Cytokines; Gene expression; Gene Knockdown Techniques; Humans; Immune system; Inflammation; Inflammation - metabolism; Laboratory animals; Mice; Mice, Inbred BALB C; mRNA; Osteosarcoma; Osteosarcoma - metabolism; Pathogens; Peroxidase; Receptors, Scavenger - genetics; Receptors, Scavenger - metabolism; Sarcoma; Software; Statistical analysis; Survival analysis; TLR4; TLR4 protein; Toll-Like Receptor 4 - genetics; Toll-Like Receptor 4 - metabolism; Toll-like receptors; Tumors
• ISSN: 0887-8013; 1098-2825
• DOI: 10.1002/jcla.23469

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. The potential mechanisms of inflammation by COLEC12 mediated through TLR4 in osteosarcoma. COLEC12 could reduce TLR4 expression, weaken NF‐κB and C3 signaling pathway to release inflammatory factors downstream, restrain immune defense to tumor cells, inhibit apoptosis of tumor cells, and cut down lives of mouses.