POU6F1, a member of the POU family of transcription factors, is involved in multiple biological processes. It can bind to specific DNA sites [8]. POU6F1 is associated with pathways related to cell proliferation, differentiation, and neural development, playing a significant role in normal biological development and disease conditions [1-7]. Genetic models, such as mouse models, are valuable for studying its functions.

In gastric cancer, overexpression of POU6F1 promotes ferroptosis by increasing lncRNA-CASC2 transcription, which in turn regulates the SOCS2/SLC7A11 signaling pathway, inhibiting cancer progression [1]. In lung adenocarcinoma, POU6F1 is downregulated, and its overexpression inhibits cell growth and invasion by binding and stabilizing RORA to suppress the HIF1A signaling pathway [2]. In sciatic nerve injury, transgenic Schwann cells overexpressing POU6F1 enhance axonal regeneration, myelination, and functional motor recovery through the JNK/c-Jun signaling pathway [3]. In the adult brain, POU6F1 is necessary for proper dendrite and synapse development in adult-born neurons in response to neuropeptide signaling [4]. In mouse pre-implantation development, the degradation of Pou6f1 by DIS3 is crucial for cell differentiation, as its persistence represses Nanog and Cdx2 transcription, disrupting the morula-to-blastocyst transition [5]. In clear cell adenocarcinoma of the ovary, POU6F1 is important for cell proliferation, and its knockdown suppresses tumor growth, suggesting it could be a new molecular target [6,7].

In summary, POU6F1 has diverse functions in different biological processes and diseases. Studies using gene-based models, especially mouse models, have revealed its role in cancer development, nerve regeneration, and embryonic development. These findings provide potential therapeutic targets for diseases like gastric and ovarian cancers, and insights into neural development and pre-implantation embryogenesis.

References:

1. Wang, Jingyun, Jia, Qiaoyu, Jiang, Shuqin, Lu, Wenquan, Ning, Hanbing. 2024. POU6F1 promotes ferroptosis by increasing lncRNA-CASC2 transcription to regulate SOCS2/SLC7A11 signaling in gastric cancer. In Cell biology and toxicology, 40, 3. doi:10.1007/s10565-024-09843-y. https://pubmed.ncbi.nlm.nih.gov/38267746/

2. Xiao, Wenjing, Geng, Wei, Zhou, Mei, Yang, Guanghai, Jin, Yang. 2022. POU6F1 cooperates with RORA to suppress the proliferation of lung adenocarcinoma by downregulation HIF1A signaling pathway. In Cell death & disease, 13, 427. doi:10.1038/s41419-022-04857-y. https://pubmed.ncbi.nlm.nih.gov/35504868/

3. Li, Wen-Yuan, Li, Zhi-Gang, Fu, Xiu-Mei, Zhu, Xiao-Feng, Wang, Ying. 2022. Transgenic Schwann cells overexpressing POU6F1 promote sciatic nerve regeneration within acellular nerve allografts. In Journal of neural engineering, 19, . doi:10.1088/1741-2552/ac9e1e. https://pubmed.ncbi.nlm.nih.gov/36317259/

4. McClard, Cynthia K, Kochukov, Mikhail Y, Herman, Isabella, Mardon, Graeme, Arenkiel, Benjamin R. 2018. POU6f1 Mediates Neuropeptide-Dependent Plasticity in the Adult Brain. In The Journal of neuroscience : the official journal of the Society for Neuroscience, 38, 1443-1461. doi:10.1523/JNEUROSCI.1641-17.2017. https://pubmed.ncbi.nlm.nih.gov/29305536/

5. Wu, Di, Dean, Jurrien. 2023. RNA exosome ribonuclease DIS3 degrades Pou6f1 to promote mouse pre-implantation cell differentiation. In Cell reports, 42, 112047. doi:10.1016/j.celrep.2023.112047. https://pubmed.ncbi.nlm.nih.gov/36724075/

6. Suzuki, Nao, Yoshioka, Norihito, Uekawa, Atsushi, Kiguchi, Kazushige, Ishizuka, Bunpei. . Transcription factor POU6F1 is important for proliferation of clear cell adenocarcinoma of the ovary and is a potential new molecular target. In International journal of gynecological cancer : official journal of the International Gynecological Cancer Society, 20, 212-9. doi:10.1111/IGC.0b013e3181c97ae0. https://pubmed.ncbi.nlm.nih.gov/20134265/

7. Yoshioka, Norihito, Suzuki, Nao, Uekawa, Atsushi, Kiguchi, Kazushige, Ishizuka, Bunpei. . POU6F1 is the transcription factor that might be involved in cell proliferation of clear cell adenocarcinoma of the ovary. In Human cell, 22, 94-100. doi:10.1111/j.1749-0774.2009.00074.x. https://pubmed.ncbi.nlm.nih.gov/19874398/

8. Wey, E, Schäfer, B W. . Identification of novel DNA binding sites recognized by the transcription factor mPOU (POU6F1). In Biochemical and biophysical research communications, 220, 274-9. doi:. https://pubmed.ncbi.nlm.nih.gov/8645295/