CYB5D2, also known as Neuferricin, is a member of the membrane-associated progesterone receptors (MAPRs) family. It binds to heme and is involved in multiple cellular processes such as cell cycle regulation, proliferation, apoptosis, and invasion. It may also interact with cytochrome P450 systems, influencing sterol synthesis and drug metabolism [3,5].

In breast cancer, CYB5D2 has tumor-suppressing functions. Its down-regulation is associated with cancer progression, as CYB5D2 overexpression induces apoptosis in MCF7 cells while knockdown enhances cell proliferation. A CYB5D2-derived 21-gene signature is strongly correlated with shortened overall survival and can independently predict breast cancer deaths [1].

In cervical cancer, CYB5D2 also acts as a tumor suppressor. Ectopic expression inhibits HeLa cell invasion and lung metastasis in mice, and knockdown enhances invasion. Additionally, its expression is reduced in cervical squamous cell carcinomas [2].

In hepatocellular carcinoma, CYB5D2 overexpression inhibits cell proliferation, migration, invasion, and epithelial-mesenchymal transition by inhibiting TGF-β expression [4].

In conclusion, CYB5D2 plays crucial tumor-suppressing roles in breast, cervical, and hepatocellular carcinomas. Functional studies, potentially including gene knockout models in the future, have revealed its importance in regulating cellular processes related to cancer progression. Understanding CYB5D2's functions provides insights into the molecular mechanisms of these cancers and may offer new therapeutic targets [1,2,4].