Plod3, or Procollagen-Lysine,2-Oxoglutarate 5-Dioxygenase 3, is a key gene coding enzymes that catalyze the lysyl hydroxylation of extracellular matrix collagen [2]. It is involved in various biological processes and is associated with the TNF-α/ NF-κB, FoxO3/Survivin, PKCδ/CDK1/LIMD1, and STAT3 pathways, playing a significant role in multiple diseases [1,2,3,5]. Genetic models, such as gene knockout (KO) or conditional knockout (CKO) mouse models, can be valuable for studying its functions.

In CRC, knockdown of Plod3 in CT26 or MC38 mouse CRC cells significantly inhibited proliferation, migration, invasion, and liver metastasis, while overexpression promoted these processes. This revealed that Plod3 facilitates T cell activation in the tumor microenvironment and affects the TNF-α/ NF-κB pathway [1].

In gastric cancer, depletion of Plod3 in Trastuzumab-resistant GC cell lines led to decreased cell proliferation, tumor growth, and increased Trastuzumab sensitivity, uncovering its role in the FoxO3/Survivin pathway related to therapy resistance [2].

In NSCLC, silencing Plod3 activated the PKCδ/CDK1/LIMD1 signaling pathway, suppressing NSCLC cell proliferation, colony formation, cell cycle entry, and apoptosis resistance both in vitro and in vivo [3].

In lung cancer, knockdown of Plod3 in lung cancer cells overcame chemoresistance and radioresistance by inducing apoptosis. In a mouse xenograft model, Plod3 knockdown promoted radiation-induced tumor growth inhibition [4]. Also, in lung cancer, Plod3 was found to promote lung metastasis by interacting with STAT3 [5].

In conclusion, Plod3 plays essential biological functions in processes like tumor cell proliferation, migration, invasion, metastasis, and therapy resistance across multiple cancers including CRC, gastric cancer, NSCLC, and lung cancer. The use of KO or CKO mouse models in these studies has been crucial in revealing these functions, providing insights into potential therapeutic targets for these diseases.