Plod3, or Procollagen-Lysine,2-Oxoglutarate 5-Dioxygenase 3, is a key gene coding enzymes that catalyze the lysyl hydroxylation of extracellular matrix collagen. It is involved in various biological processes and associated with multiple pathways, such as the TNF-α/ NF-κB pathway, FoxO3/Survivin pathway, and is related to genomic instability and immune cell infiltration [1,2,3].

In colorectal cancer (CRC), different liver metastasis models using PLOD3 stable knockdown or overexpression CT26 or MC38 mouse CRC cells showed that PLOD3 promotes liver metastasis and tumor progression, and facilitates T cell activation in the tumor microenvironment [1]. In gastric cancer, depletion of PLOD3 in Trastuzumab resistant GC cell lines led to decreased cell proliferation and increased Trastuzumab sensitivity [2]. In colon adenocarcinoma, high PLOD3 expression was associated with unfavorable prognosis, genomic instability, and reduced immune cell infiltrating levels [3].

In conclusion, PLOD3 plays essential roles in the progression and metastasis of multiple cancers, such as CRC and gastric cancer. Gene knockout or knockdown models in mice have been crucial in revealing these functions, highlighting PLOD3 as a potential target for translational medicine and cancer treatment.

References:

1. Ding, Min, Wang, Cheng, Hu, Junhong, Wu, Wenlan, Xia, Hongping. 2024. PLOD3 facilitated T cell activation in the colorectal tumor microenvironment and liver metastasis by the TNF-α/ NF-κB pathway. In Journal of translational medicine, 22, 30. doi:10.1186/s12967-023-04809-w. https://pubmed.ncbi.nlm.nih.gov/38184566/

2. Chen, Yueda, Ye, Botian, Wang, Chunyan, Qin, Jing, Shen, Zhenbin. 2022. PLOD3 contributes to HER-2 therapy resistance in gastric cancer through FoxO3/Survivin pathway. In Cell death discovery, 8, 321. doi:10.1038/s41420-022-01103-4. https://pubmed.ncbi.nlm.nih.gov/35835735/

3. Deng, Xianyu, Pan, Yun, Yang, Muqing, Liu, Ying, Li, Jiyu. 2021. PLOD3 Is Associated with Immune Cell Infiltration and Genomic Instability in Colon Adenocarcinoma. In BioMed research international, 2021, 4714526. doi:10.1155/2021/4714526. https://pubmed.ncbi.nlm.nih.gov/34239923/