Plod3, short for Procollagen-Lysine,2-Oxoglutarate 5-Dioxygenase 3, is a key gene coding enzymes that catalyze the lysyl hydroxylation of extracellular matrix collagen [2,4]. It is involved in various biological processes such as tissue remodeling and fibrosis [6]. Associated pathways include the TNF-α/NF-κB pathway [1], FoxO3/Survivin pathway [2], PKCδ/CDK1/LIMD1 signaling pathway [5], and it interacts with STAT3 [7]. Genetic models, especially KO/CKO mouse models, play a crucial role in studying its functions.

In colorectal cancer (CRC), knockdown of Plod3 in mouse models using CT26 or MC38 cells significantly inhibited proliferation, migration, invasion, and liver metastasis, while overexpression promoted these processes. It also facilitated T cell activation in the tumor microenvironment via the TNF-α/NF-κB pathway [1]. In gastric cancer, depletion of Plod3 in cell lines led to decreased cell proliferation, tumor growth, and increased Trastuzumab sensitivity, and in patients, high Plod3 expression correlated with decreased therapy responsiveness [2]. In colon adenocarcinoma, high Plod3 expression was associated with unfavorable prognosis, genomic instability, and reduced immune cell infiltration [3]. In non-small cell lung cancer, silencing Plod3 in vitro and in vivo experiments suppressed cell proliferation, colony formation, cell cycle entry, and resistance to apoptosis by activating the PKCδ/CDK1/LIMD1 signaling pathway [5]. In lung cancer, Plod3 knockdown overcame chemoresistance and radioresistance in cells and promoted radiation-induced tumor growth inhibition in a mouse xenograft model [6], and overexpression promoted lung metastasis by interacting with STAT3 [7].

In conclusion, Plod3 is essential in multiple disease-related biological processes. Studies using KO/CKO mouse models and other loss-of-function experiments have revealed its roles in promoting tumor progression and metastasis in cancers like CRC, gastric cancer, and lung cancer. Understanding Plod3 functions through these models provides potential therapeutic targets for these malignancies.