E2f6, a member of the E2F transcription factor family, plays diverse and crucial roles. It is involved in the regulation of a wide variety of genes through activation and repression, and is associated with pathways like the E2F/Rb pathway which regulates cell growth, differentiation, and death [3,4]. E2f6 is also part of the polycomb repressive complex 1.6 (PRC1.6), contributing to epigenetic regulation [2]. Genetic models, such as gene knockout in mice, are valuable for studying its functions.

In mouse development, E2f6 inactivation leads to a failure to deposit CpG island DNA methylation at germline genes during implantation, highlighting its role in initiating stable epigenetic silencing of germline genes in early embryogenesis [2]. In breast cancer cells, RNA interference-mediated depletion of E2f6 reduces cell viability, especially during replication stress, suggesting it could be a target for combined therapy [3]. In cardiomyocytes, modulation of E2F6 levels can affect drug-induced apoptosis, with E2F6 having an anti-apoptotic potential [4]. In various cancers like glioblastoma multiforme, gastric carcinoma, ovarian cancer, and glioma, E2f6 expression is related to tumor progression, prognosis, and can regulate processes like cell proliferation, invasion, and apoptosis [1,5,6,7]. For example, in gastric carcinoma, E2F6-mediated down-regulation of lncRNA CASC2 promotes cancer progression [5].

In conclusion, E2f6 is essential for multiple biological processes including embryonic development and cell survival during stress. Its role in various disease areas, especially cancer, is significant as demonstrated through gene knockout and other functional studies. These studies help in understanding the mechanisms underlying disease development and potentially identifying E2f6 as a therapeutic target.

References:

1. Gong, Chuandong, Tu, Zewei, Long, Xiaoyan, Li, Jingying, Huang, Kai. 2023. Predictive role of E2F6 in cancer prognosis and responses of immunotherapy. In International immunopharmacology, 127, 111302. doi:10.1016/j.intimp.2023.111302. https://pubmed.ncbi.nlm.nih.gov/38071912/

2. Dahlet, Thomas, Truss, Matthias, Frede, Ute, Hagemeier, Christian, Weber, Michael. 2021. E2F6 initiates stable epigenetic silencing of germline genes during embryonic development. In Nature communications, 12, 3582. doi:10.1038/s41467-021-23596-w. https://pubmed.ncbi.nlm.nih.gov/34117224/

3. Lafta, Inam Jasim. 2019. E2F6 is essential for cell viability in breast cancer cells during replication stress. In Turkish journal of biology = Turk biyoloji dergisi, 43, 293-304. doi:10.3906/biy-1905-6. https://pubmed.ncbi.nlm.nih.gov/31768102/

4. Major, Jennifer L, Salih, Maysoon, Tuana, Balwant S. 2017. E2F6 protein levels modulate drug induced apoptosis in cardiomyocytes. In Cellular signalling, 40, 230-238. doi:10.1016/j.cellsig.2017.09.022. https://pubmed.ncbi.nlm.nih.gov/28964969/

5. Li, Yingxia, Jiang, Libin, Lv, Shuai, He, Yixin, Wen, Hongtao. 2019. E2F6-mediated lncRNA CASC2 down-regulation predicts poor prognosis and promotes progression in gastric carcinoma. In Life sciences, 232, 116649. doi:10.1016/j.lfs.2019.116649. https://pubmed.ncbi.nlm.nih.gov/31301415/

6. Cheng, Frank H C, Lin, Hon-Yi, Hwang, Tzy-Wei, Tsai, Je-Chiang, Chan, Michael W Y. 2019. E2F6 functions as a competing endogenous RNA, and transcriptional repressor, to promote ovarian cancer stemness. In Cancer science, 110, 1085-1095. doi:10.1111/cas.13920. https://pubmed.ncbi.nlm.nih.gov/30582655/

7. Liu, Liang, Li, Xiaojian, Wu, Heming, Li, Xiang, Shi, Yan. 2021. The COX10-AS1/miR-641/E2F6 Feedback Loop Is Involved in the Progression of Glioma. In Frontiers in oncology, 11, 648152. doi:10.3389/fonc.2021.648152. https://pubmed.ncbi.nlm.nih.gov/34381702/