Inactivating ARID1A tumor suppressor enhances TERT transcription and maintains telomere length in cancer cells

Yohan Suryo Rahmanto, Jin Gyoung Jung, Ren Chin Wu, Yusuke Kobayashi, Christopher M. Heaphy, Alan K. Meeker, Tian Li Wang, Ie Ming Shih

研究成果: Article査読

21 被引用数 (Scopus)

抄録

ARID1A is a tumor suppressor gene that belongs to the switch/sucrose non-fermentable chromatin remodeling gene family. It is mutated in many types of human cancer with the highest frequency in endometrium-related ovarian and uterine neoplasms including ovarian clear cell, ovarian endometrioid, and uterine endometrioid carcinomas. We have previously reported that mutations in the promoter of human telomerase reverse transcriptase (TERT) rarely co-occur with the loss of ARID1A protein expression, suggesting a potential role of ARID1A in telomere biology. In this study, we demonstrate that ARID1A negatively regulates TERT transcriptional regulation and activity via binding to the regulatory element of TERT and promotes a repressive histone mode. Induction of ARID1A expression was associated with increased occupancy of SIN3A and H3K9me3, known transcription repressor and histone repressor marks, respectively. Thus, loss of ARID1A protein expression caused by inactivating mutations reactivates TERT transcriptional activity and confers a survival advantage of tumor cells by maintaining their telomeres.

本文言語English
ページ(範囲)9690-9699
ページ数10
ジャーナルJournal of Biological Chemistry
291
18
DOI
出版ステータスPublished - 2016

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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