OCT4 directly regulates stemness and extracellular matrix-related genes in human germ cell tumours

Bomin Song, Dong Keon Kim, Jihoon Shin, Seung Hyun Bae, Hee Yeon Kim, Bomyi Won, Jong Kwang Kim, Hong Duk Youn, Seong Tae Kim, Sang Won Kang, Hyonchol Jang

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

Germ cell tumours (GCTs) are one of the most threatening malignancies in young men and women. Although several reports have suggested the importance of OCT4 in human GCTs, its role has not been clearly investigated on a molecular level. In this study, we revealed GCT-specific direct transcriptional target genes of OCT4. Conditional knockdown of OCT4 in GCT cell lines reduced cell proliferation by affecting both cell cycle and death. Knockdown of OCT4 also reduced stemness of GCTs, as assessed by the expression of other stemness factors, alkaline phosphatase staining, and tumour sphere formation ability. Analysis of whole mRNA expression patterns among GCT cells harbouring endogenous, depleted, and rescued OCT4 revealed 1133 OCT4 target genes in GCT. Combined analysis of both the chromatin binding signature of OCT4 and the genes whose expression levels were changed by OCT4 revealed 258 direct target genes of OCT4 in GCTs. In a similar way, 594 direct target genes in normal embryonic stem cells (ESCs) were identified. Among these two sets of OCT4 direct target genes, 38 genes were common between GCTs and ESCs, most of which were related to regulation of pluripotency, and 220 genes were specific to GCTs, most of which were related to focal adhesion and extracellular matrix organisation. These results provide a molecular basis for how OCT4 regulates GCT stemness and will aid our understanding of the role of OCT4 in other cancers.

Original languageEnglish
Pages (from-to)1980-1986
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume503
Issue number3
DOIs
StatePublished - 10 Sep 2018

Keywords

  • Germ cell tumour
  • OCT4
  • Stemness
  • Transcription factor

Cite this

Song, B., Kim, D. K., Shin, J., Bae, S. H., Kim, H. Y., Won, B., Kim, J. K., Youn, H. D., Kim, S. T., Kang, S. W., & Jang, H. (2018). OCT4 directly regulates stemness and extracellular matrix-related genes in human germ cell tumours. Biochemical and Biophysical Research Communications, 503(3), 1980-1986. https://doi.org/10.1016/j.bbrc.2018.07.145