Hipk3, short for homeodomain-interacting protein kinase 3, is a gene whose protein product may be involved in multiple biological processes. It has been associated with various pathways such as the mTOR and Wnt pathways which are crucial in cell proliferation and movement [3]. In the context of disease, Hipk3 is of significant importance, especially in cancer research where its dysregulation has been linked to tumor development [1,2,3,4].

In gastric cancer, knockdown of Hipk3 in in vitro and in vivo experiments enhanced tumor proliferation and metastasis, indicating its role in preventing disease progression and maintaining sensitivity to platinum drugs. The myocyte enhancer factor 2C (MEF2C) was identified as a transcriptional regulator of Hipk3, and Hipk3 was found to down-regulate the morphogenesis regulator microtubule-associated protein (MAP7) through ubiquitination [3].

In colorectal cancer, exosomal hsa-miR-101-3p was shown to inhibit Hipk3, and overexpression of Hipk3 in HCT116 and SW480 cells led to retarded cell growth, migration, increased sensitivity to 5-FU, along with changes in metabolic parameters like increased mitochondrial membrane potential, more reactive oxygen species production, more mitochondria, and decreased glycolysis [4].

In cardiomyocytes, miR-21 was found to attenuate FAS-mediated apoptosis by regulating Hipk3 expression, with Hipk3 down-regulation decreasing FAS-mediated apoptosis by inhibiting FADD phosphorylation and subsequent changes in apoptosis-related proteins [5].

In conclusion, Hipk3 plays essential roles in maintaining normal cellular functions and preventing disease progression in multiple disease areas. Its function in cancer, especially in gastric and colorectal cancer, and in cardiomyocyte apoptosis regulation has been well-demonstrated through in vitro and in vivo functional studies. These findings from model-based research, including cell-based in vitro models and in vivo mouse-like models, provide valuable insights into the mechanisms of disease and potential therapeutic targets related to Hipk3.