Dcn, also known as decorin, is a member of the small leucine-rich proteoglycan gene family. It is secreted from stromal fibroblasts and has non-cell-autonomous anti-cancer effects. Dcn is involved in multiple biological processes, such as immune responses, and may play a role in pathways like NFKB-dependent cytokine production [1,2].

In ferroptosis, Dcn is released by dying cells through autophagy and lysosomal exocytosis, then binds to AGER on macrophages to trigger pro-inflammatory cytokine production. Inhibition of the DCN-AGER axis protects against ferroptotic death-related acute pancreatitis [1]. In breast stromal fibroblasts, DCN down-regulation activates them and promotes pro-carcinogenic effects through the IL-6/STAT3/AUF1 signaling [2]. In renal cell carcinoma, DCN overexpression inhibits cell proliferation and metastasis by upregulating P21 and E-cadherin [3]. Also, in cervical cancer, lncRNA PGM5-AS1 can upregulate DCN by sponging miR-4284, inhibiting cancer cell malignancy [4].

In conclusion, Dcn is essential in multiple biological processes and diseases. Its role in immune responses during ferroptosis, and its anti-carcinogenic effects in breast and renal cancers highlight its significance. Functional studies, especially those using gene-knockout models (implied by loss-of-function experiments), have been crucial in revealing Dcn's functions in these disease conditions.

References:

1. Liu, Jiao, Zhu, Shan, Zeng, Ling, Tang, Daolin, Kang, Rui. 2021. DCN released from ferroptotic cells ignites AGER-dependent immune responses. In Autophagy, 18, 2036-2049. doi:10.1080/15548627.2021.2008692. https://pubmed.ncbi.nlm.nih.gov/34964698/

2. Aljagthmi, Wafaa A, Alasmari, Manal A, Daghestani, Maha H, Al-Mohanna, Falah H, Aboussekhra, Abdelilah. 2024. Decorin (DCN) Downregulation Activates Breast Stromal Fibroblasts and Promotes Their Pro-Carcinogenic Effects through the IL-6/STAT3/AUF1 Signaling. In Cells, 13, . doi:10.3390/cells13080680. https://pubmed.ncbi.nlm.nih.gov/38667295/

3. Xu, Yongcan, Xia, Qiuyuan, Rao, Qiu, Chen, Hui, Zhou, Xiaojun. 2015. DCN deficiency promotes renal cell carcinoma growth and metastasis through downregulation of P21 and E-cadherin. In Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine, 37, 5171-83. doi:10.1007/s13277-015-4160-1. https://pubmed.ncbi.nlm.nih.gov/26547587/

4. Wang, Huimin, Wang, Dan, Wei, Qiong, Li, Chunyan, Yang, Jing. . Long non-coding RNAs PGM5-AS1 upregulates Decorin (DCN) to inhibit cervical cancer progression by sponging miR-4284. In Bioengineered, 13, 9872-9884. doi:10.1080/21655979.2022.2062088. https://pubmed.ncbi.nlm.nih.gov/35420507/