Kmt5a, also known as lysine methyltransferase 5A, is an enzyme that catalyzes the mono-methylation of histone H4 lysine 20 and non-histone proteins. It is involved in multiple biological processes and signaling pathways, playing a significant role in maintaining genome integrity, cell metabolism, and cell proliferation [3,5,6].

In various cancers, Kmt5a knockdown has shown inhibitory effects. In osteosarcoma cells, knockdown of Kmt5a inhibited cell proliferation, enhanced cell death, and suppressed migration and invasion through β-catenin signalling [2]. In clear cell renal cell carcinoma, in vitro knockdown of Kmt5A expression in 786-O cells inhibited cell migration and invasion, and Kmt5A reduced cadherin-1 protein levels by directly inhibiting its transcription [4]. In breast cancer, Kmt5a knockdown upregulated FBP1 related to glucose metabolism, and Kmt5a was shown to induce chemotherapy resistance by promoting cell proliferation and glycolysis [6]. In addition, in triple-negative breast cancer, Kmt5A-methylated SNIP1 promoted cancer metastasis by activating YAP signaling [1]. In non-small-cell lung cancer, Kmt5A-mediated di-methylation of CD147-K234 promoted cancer progression by enhancing lactate export [3].

In conclusion, Kmt5a plays a crucial role in the development and progression of multiple cancers, as well as in processes like endothelial-to-mesenchymal transition in diabetic nephropathy. Gene knockout or knockdown models of Kmt5a have been instrumental in revealing its role in these disease conditions, providing potential therapeutic targets for treatment.