Hoxc4, a member of the homeobox family, functions as a transcription factor regulating morphological development. It is involved in various biological processes and associated with multiple pathways such as NF-κB signaling, TGF-β/SMAD signaling, and is crucial for immunoglobulin class-switch recombination and somatic hypermutation [1,3,4,6]. It also plays a role in hematopoiesis and cell differentiation [3,7].

In pancreatic cancer, knockdown of Hoxc4 reduced cell proliferation, increased apoptosis, and caused G1 phase arrest, indicating its role in promoting cancer cell growth through LDHA-mediated glycolysis [1]. In Chiari malformations, a candidate variant in Hoxc4 was identified in high-risk pedigrees, with the mutation potentially reducing its binding affinity to DNA [2]. In breast cancer, the lncRNA XIST/miR-455-3p/Hoxc4 axis promotes cancer development by activating the TGF-β/SMAD pathway [4]. In prostate cancer, HOXC4 and HOXC6 may compete with HOXB13 for binding sites, altering the transcriptome [5]. In acute promyelocytic leukemia cells, upregulated Hoxc4 induces CD14 expression during differentiation [7]. And HOXC4 homeoprotein can expand human hematopoietic stem cells [8].

In conclusion, Hoxc4 is essential in regulating diverse biological processes and is implicated in multiple disease conditions. Studies, especially those using gene-knockdown approaches, have revealed its roles in cancer cell proliferation, development of Chiari malformations, hematopoiesis, and cell differentiation, providing insights into potential therapeutic targets for these diseases.