Zbtb7b, also known as Th-inducing POZ-Kruppel factor (ThPOK), is a transcription factor that plays diverse and crucial roles in multiple biological processes. It is involved in pathways related to cell differentiation, inflammation, metabolism, and tumorigenesis, thereby being of great biological importance. Genetic models, especially knockout (KO) and conditional knockout (CKO) mouse models, have been instrumental in uncovering its functions [4,5].

In hepatocarcinogenesis, hepatocyte-specific knockout of Zbtb7b in mouse models promotes HCC development induced by activated Akt and N-Ras. Zbtb7b deficiency also sensitizes hepatocytes to Akt-induced oncogenic transformation and HCC initiation. Mechanistically, Zbtb7b directly regulates c-Jun, and knockdown of c-Jun delays HCC development in Zbtb7b-deficient livers [1]. In metabolic dysfunction-associated steatotic liver disease (MASLD)-related HCC, Zbtb7b knockout mouse models show that Zbtb7b is compensatively increased during MASLD progression to restrict lipid deposition, protecting against HCC initiation by suppressing the long noncoding RNA H19 [3]. In radiation-induced lung injury, silencing Zbtb7b in THP1 cells and BEAS-2B lung bronchial epithelial cells leads to higher radiation-induced IL-6 production. Zbtb7b recruits RNA demethylase ALKBH5 to IL6 mRNA, inhibiting its m6A modification and nuclear export [2]. In ulcerative colitis, over-expression of Zbtb7b in a DSS-induced colitis model activates CD4+T cell maturation, represses the differentiation of double-positive CD4+CD8+T cells, and contributes to the production of inflammatory cytokines [4].

In conclusion, Zbtb7b is a key regulator in multiple biological processes. Through KO/CKO mouse models, its functions in tumorigenesis, such as in hepatocellular carcinoma, and in inflammatory diseases like radiation-induced lung injury and ulcerative colitis, have been revealed. These findings provide potential targets for disease treatment in these areas.