2. Academic Validation
  3. E2F8 Transcriptionally Activates DTL to Promote Endometrial Cancer Progression Via the MAPK Pathway

E2F8 Transcriptionally Activates DTL to Promote Endometrial Cancer Progression Via the MAPK Pathway

  • Reprod Sci. 2025 Dec 29. doi: 10.1007/s43032-025-02040-0.
Wenkang Tao 1,  Jiaqi Pan 2,  Wenqin Zhang 3,  Yueyue Huang 3 4,  Fenglin Bi 1,  Xuemei Ding 1,  Yuyun Jiang 1,  Yuqian Ma 3 4,  Yi Yang 4 5,  Jifang Shi 6 7
Affiliations

Affiliations

  • 1 Department of Gynecology, The First Affiliated Hospital of Dali University (Yunnan Provincial Fourth People's Hospital, Yunnan Provincial Second Infectious Disease Hospital), Dali, Yunnan, 671000, P.R. China.
  • 2 Department of Obstetrics and Gynecology, Huizhou Central People's Hospital, Huizhou, Guangdong, 516000, P.R. China.
  • 3 Department of Obstetrics and Gynecology, The First Affiliated Hospital of Dali University (Yunnan Provincial Fourth People's Hospital, Yunnan Provincial Second Infectious Disease Hospital), No. 32, Carlsberg Avenue, Dali, Yunnan, 671000, P.R. China.
  • 4 Department of Clinical Medicine, Dali University, Dali, Yunnan, 671000, P.R. China.
  • 5 Department of Anesthesiology, The First Affiliated Hospital of Dali University (Yunnan Provincial Fourth People's Hospital, Yunnan Provincial Second Infectious Disease Hospital), Dali, Yunnan, 671000, P.R. China.
  • 6 Department of Obstetrics and Gynecology, The First Affiliated Hospital of Dali University (Yunnan Provincial Fourth People's Hospital, Yunnan Provincial Second Infectious Disease Hospital), No. 32, Carlsberg Avenue, Dali, Yunnan, 671000, P.R. China. [email protected].
  • 7 Department of Clinical Medicine, Dali University, Dali, Yunnan, 671000, P.R. China. [email protected].
PMID: 41461624 DOI: 10.1007/s43032-025-02040-0
Abstract

E2F family transcription factors are involved in various cancers, yet the role of E2F transcription factor 8 (E2F8) in endometrial Cancer (EC) remains elusive. This study explores how E2F8 transcriptionally activates denticleless E3 ubiquitin protein Ligase homolog (DTL) to promote EC progression via the MAPK signaling. Bioinformatic analysis of the GEO dataset GSE63678, along with GEPIA2, AnimalTFDB v4, and ChIP-Atlas, identified E2F8 and its potential target DTL in EC. Elevated expression of E2F8 and DTL was confirmed in EC tissues, which correlated with a higher International Federation of Gynecology and Obstetrics stage. Functional assays demonstrated that E2F8 knockdown suppressed EC cell proliferation, migration, invasion, and MAPK pathway activation, while DTL overexpression or PDCD4 knockdown reversed these effects. Knockdown of DTL enhanced PDCD4 ubiquitination. In vivo, silencing of E2F8 inhibited tumor growth in EC xenograft models, whereas DTL upregulation or PDCD4 knockdown restored tumor progression and enhanced MAPK pathway activity and Ki67 expression. In conclusion, E2F8 promotes EC progression by transcriptionally activating DTL and activating the MAPK pathway. These findings provide novel mechanistic insights into EC progression and suggest that the E2F8/DTL/PDCD4/MAPK axis may serve as a potential therapeutic target for EC.

Keywords

DTL; E2F8; EC; MAPK pathway; PDCD4 ubiquitination.

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