Cux2, short for Cut-like homeobox 2, is a transcription factor that plays diverse and crucial roles in various biological processes. It is involved in regulating neuronal proliferation, dendrite branching, and synapse formation, especially in the upper-cortical layers [4,5]. In limb development, it refines the forelimb field by controlling the expression of genes like Raldh2 and Hox genes [6]. Additionally, it is important for neurogenesis in the olfactory epithelium [7]. Genetic models, such as gene knockout mouse models, are valuable tools for studying its functions.

In disease-related studies, in breast cancer, CUX2 promotes tumorigenesis and progression. Inhibition of CUX2 suppresses breast cancer cell malignant phenotypes through the KDM5B/SOX17 axis [1]. In gliomas, CUX2 has low expression, and its overexpression represses glioma cell proliferation, migration, and invasion by enhancing ADCY1 transcription [2]. In papillary thyroid cancer, CUX2 functions as an oncogene, and its silencing inhibits cell proliferation, colony formation, migration, invasion, and induces apoptosis [3]. In epilepsy, Cux2 deficiency causes facilitation of excitatory synaptic transmission onto the hippocampus and increases seizure susceptibility to kainate [4].

In conclusion, Cux2 is essential for normal neuronal and limb development. Its dysregulation is associated with multiple diseases, including breast cancer, gliomas, papillary thyroid cancer, and epilepsy. The use of gene knockout mouse models has been instrumental in uncovering its role in these biological processes and disease conditions, providing insights into potential therapeutic targets.

References:

1. Li, Lili, Zhu, Genbao, Tan, Kemeng, Chen, Jie, Ma, Chengquan. . CUX2/KDM5B/SOX17 Axis Affects the Occurrence and Development of Breast Cancer. In Endocrinology, 163, . doi:10.1210/endocr/bqac110. https://pubmed.ncbi.nlm.nih.gov/35881915/

2. Yao, Guojun, Le, Shihai, Min, Sufang, Cai, Chuanxing, Deng, Ling. 2022. CUX2 prevents the malignant progression of gliomas by enhancing ADCY1 transcription. In Experimental brain research, 240, 3153-3165. doi:10.1007/s00221-022-06481-w. https://pubmed.ncbi.nlm.nih.gov/36242624/

3. Sun, Yihan, Ye, Danrong, Li, Yuefeng, Wang, Ouchen, Zhang, Xiaohua. 2018. CUX2 functions as an oncogene in papillary thyroid cancer. In OncoTargets and therapy, 12, 217-224. doi:10.2147/OTT.S185710. https://pubmed.ncbi.nlm.nih.gov/30636884/

4. Suzuki, Toshimitsu, Tatsukawa, Tetsuya, Sudo, Genki, Moore, Adrian Walton, Yamakawa, Kazuhiro. 2022. CUX2 deficiency causes facilitation of excitatory synaptic transmission onto hippocampus and increased seizure susceptibility to kainate. In Scientific reports, 12, 6505. doi:10.1038/s41598-022-10715-w. https://pubmed.ncbi.nlm.nih.gov/35581205/

5. Yang, Hayoung, Kim, Jiwoo, Kim, Yujin, Sestan, Nenad, Shim, Sungbo. 2019. Cux2 expression regulated by Lhx2 in the upper layer neurons of the developing cortex. In Biochemical and biophysical research communications, 521, 874-879. doi:10.1016/j.bbrc.2019.11.004. https://pubmed.ncbi.nlm.nih.gov/31708105/

6. Ueda, Shogo, Cordeiro, Ingrid Rosenburg, Moriyama, Yuuta, Shirahige, Katsuhiko, Tanaka, Mikiko. 2019. Cux2 refines the forelimb field by controlling expression of Raldh2 and Hox genes. In Biology open, 8, . doi:10.1242/bio.040584. https://pubmed.ncbi.nlm.nih.gov/30651234/

7. Wittmann, Walter, Iulianella, Angelo, Gunhaga, Lena. 2014. Cux2 acts as a critical regulator for neurogenesis in the olfactory epithelium of vertebrates. In Developmental biology, 388, 35-47. doi:10.1016/j.ydbio.2014.01.026. https://pubmed.ncbi.nlm.nih.gov/24512687/