Zc3h15, also known as developmentally regulated GTP-binding protein 1 (DRG1) family regulatory protein 1 (DFRP1), is a highly conserved eukaryotic protein. It is involved in multiple cellular processes, associated with the NF-κB pathway through interaction with TRAF-2 [4]. Zc3h15 is also linked to active translation machinery and has been implicated in fundamental cellular processes like cell growth, transcription, and cell adhesion [2,4]. Genetic models can be crucial for further exploring its detailed functions.

In melanoma, knockdown of Zc3h15 inhibited cell proliferation, induced cell cycle arrest at G0/G1 phase, and decreased the expression of cell cycle-related proteins (CDK4, CDK6, CCND1), while increasing p21. It also reduced the migration and invasion abilities of melanoma cells, both in vitro and in vivo [1].

In bone cancer pain murine models, silencing ZC3H15 with AAV-shZC3H15 alleviated pain progression, improved neuronal oxidative stress by mediating the KEAP1/NRF2 pathway, and attenuated microglial activation and inflammatory response by blocking the IκBα/NF-κB signaling pathway [3].

In conclusion, Zc3h15 plays important roles in multiple biological processes and diseases. In melanoma, it promotes cell proliferation, migration, invasion, and tumorigenicity. In bone cancer pain, it is involved in neuronal oxidative stress and microglial inflammation. The study of Zc3h15 using gene-knockdown models helps to understand its functions in these disease-related processes, potentially providing new targets for treatment.