OCT4 directly regulates sternness and extracellular matrix-related genes in human germ cell tumours
- 주제(키워드) OCT4 , Stemness , Germ cell tumour , Transcription factor
- 주제(기타) Biochemistry & Molecular Biology; Biophysics
- 설명문(일반) [Song, Bomin; Kim, Dong Keon; Bae, Seung-Hyun; Kim, Hee Yeon; Won, Bomyi; Kim, Jong Kwang; Jang, Hyonchol] Natl Canc Ctr, Res Inst, Goyang 10408, South Korea; [Song, Bomin; Kang, Sang Won] Ewha Womans Univ, Dept Life Sci, Seoul 03760, South Korea; [Kim, Dong Keon; Kim, Seong-Tae] Sungkyunkwan Univ, Dept Mol Cell Biol, Sch Med, Suwon 16419, South Korea; [Shin, Jihoon; Youn, Hong-Duk] Seoul Natl Univ, Natl Creat Res Ctr, Dept Biomed Sci, Epigen Reprogramming Network,Coll Med, Seoul 03080, South Korea; [Kim, Hee Yeon; Won, Bomyi; Jang, Hyonchol] Natl Canc Ctr, Dept Canc Biomed Sci, Grad Sch Canc Sci & Policy, Goyang 10408, South Korea
- 등재 SCIE, SCOPUS
- 발행기관 ACADEMIC PRESS INC ELSEVIER SCIENCE
- 발행년도 2018
- URI http://www.dcollection.net/handler/ewha/000000155949
- 본문언어 영어
- Published As http://dx.doi.org/10.1016/j.bbrc.2018.07.145
초록/요약
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 sternness of GCTs, as assessed by the expression of other sternness factors, alkaline phosphatase staining, and tumour sphere formation ability. Analysis of whole mRNA expression patterns among GOT 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 sternness and will aid our understanding of the role of OCT4 in other cancers. (C) 2018 Elsevier Inc. All rights reserved.
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