Arid4b, a chromatin protein, is a member of the Sin3a corepressor complex. It plays a crucial role in coordinating gene expression during cell differentiation. It is associated with pathways like PI3K/AKT and is involved in important biological processes such as cell cycle regulation, apoptosis, and embryonic stem cell differentiation [1,2,3,4,5,6,7,8,9]. Genetic models, especially knockout models, have been instrumental in understanding its functions.

In glioma cells, Arid4b knockdown suppresses cell proliferation, induces G1 phase arrest and apoptosis via the PI3K/AKT pathway, and reduces cell migration and invasion, suggesting it acts as an oncogene [1]. In mouse embryonic stem cells, Arid4b-deficient cells show altered cell cycle dynamics during differentiation, with less proliferative capacity and a slight increase in early apoptosis [2]. Heterozygous knockout of ARID4B in breast cancer MCF-7 cells reduces cell proliferation and migration and affects multiple cancer-associated pathways [4].

In conclusion, Arid4b is essential for regulating cell cycle, apoptosis, and differentiation. Studies using gene knockout models have revealed its role in cancer development, including glioma and breast cancer, highlighting its potential as a therapeutic target in these disease areas.

References:

1. Luo, Siou-Min, Tsai, Wen-Chiuan, Tsai, Chia-Kuang, Chen, Ying, Hueng, Dueng-Yuan. 2021. ARID4B Knockdown Suppresses PI3K/AKT Signaling and Induces Apoptosis in Human Glioma Cells. In OncoTargets and therapy, 14, 1843-1855. doi:10.2147/OTT.S286837. https://pubmed.ncbi.nlm.nih.gov/33732001/

2. GÜven, Gözde, Terzİ ÇİzmecİoĞlu, Nihal. 2021. Arid4b alters cell cycle and cell death dynamics during mouse embryonic stem cell differentiation. In Turkish journal of biology = Turk biyoloji dergisi, 45, 56-64. doi:10.3906/biy-2009-6. https://pubmed.ncbi.nlm.nih.gov/33597822/

3. Keskin, Ezgi Gül, Huang, Jialiang, Terzi Çizmecioğlu, Nihal. 2021. Arid4b physically interacts with Tfap2c in mouse embryonic stem cells. In Turkish journal of biology = Turk biyoloji dergisi, 45, 162-170. doi:10.3906/biy-2010-67. https://pubmed.ncbi.nlm.nih.gov/33907498/

4. Gonzalez-Salinas, Fernando, Herrera-Gamboa, Jessica, Rojo, Rocio, Trevino, Victor. 2023. Heterozygous Knockout of ARID4B Using Nuclease technology Attenuates Some Aggressive Phenotypes in a Breast Cancer Cell Line. In Genes, 14, . doi:10.3390/genes14122184. https://pubmed.ncbi.nlm.nih.gov/38137006/

5. Terzi Çizmecioğlu, Nihal. . ARID4B loss leads to activated STAT1-dependent interferon pathway in mouse embryonic stem cells and during meso/endodermal differentiation. In Journal of the Turkish German Gynecological Association, 24, 187-196. doi:10.4274/jtgga.galenos.2023.2023-7-5. https://pubmed.ncbi.nlm.nih.gov/37675520/

6. Terzi Cizmecioglu, Nihal, Huang, Jialiang, Keskin, Ezgi G, Chen, Fei, Orkin, Stuart H. . ARID4B is critical for mouse embryonic stem cell differentiation towards mesoderm and endoderm, linking epigenetics to pluripotency exit. In The Journal of biological chemistry, 295, 17738-17751. doi:10.1074/jbc.RA120.015534. https://pubmed.ncbi.nlm.nih.gov/33454011/

7. Akaoka, Munetoshi, Yanagaki, Mitsuru, Kubota, Hoshiho, Shimoda, Masayuki, Ikegami, Toru. 2025. ARID4B Promotes the Progression of Hepatocellular Carcinoma Through the PI3K/AKT Pathway. In Annals of surgical oncology, 32, 3009-3018. doi:10.1245/s10434-024-16790-9. https://pubmed.ncbi.nlm.nih.gov/39751985/

8. Hao, Qi, Wang, Lulu, Zhang, Minghui, Li, Meng, Gao, Xuejun. 2021. Taurine stimulates protein synthesis and proliferation of C2C12 myoblast cells through the PI3K-ARID4B-mTOR pathway. In The British journal of nutrition, 128, 1875-1886. doi:10.1017/S0007114521004918. https://pubmed.ncbi.nlm.nih.gov/34881695/

9. Wu, Ray-Chang, Young, In-Chi, Chen, Yu-Fang, Toubaji, Antoun, Wu, Mei-Yi. 2019. Identification of the PTEN-ARID4B-PI3K pathway reveals the dependency on ARID4B by PTEN-deficient prostate cancer. In Nature communications, 10, 4332. doi:10.1038/s41467-019-12184-8. https://pubmed.ncbi.nlm.nih.gov/31551414/