RRC ID 76403
著者 Ferrari AJ, Rawat P, Rendulich HS, Annapragada AV, Kinose Y, Zhang X, Devins K, Budina A, Scharpf RB, Mitchell MA, Tanyi JL, Morgan MA, Schwartz LE, Soong TR, Velculescu VE, Drapkin R.
タイトル H2Bub1 loss is an early contributor to clear cell ovarian cancer progression.
ジャーナル JCI Insight
Abstract Epigenetic aberrations, including posttranslational modifications of core histones, are major contributors to cancer. Here, we define the status of histone H2B monoubiquitylation (H2Bub1) in clear cell ovarian carcinoma (CCOC), low-grade serous carcinoma, and endometrioid carcinomas. We report that clear cell carcinomas exhibited profound loss, with nearly all cases showing low or negative H2Bub1 expression. Moreover, we found that H2Bub1 loss occurred in endometriosis and atypical endometriosis, which are established precursors to CCOCs. To examine whether dysregulation of a specific E3 ligase contributes to the loss of H2Bub1, we explored expression of ring finger protein 40 (RNF40), ARID1A, and UBR7 in the same case cohort. Loss of RNF40 was significantly and profoundly correlated with loss of H2Bub1. Using genome-wide DNA methylation profiles of 230 patients with CCOC, we identified hypermethylation of RNF40 in CCOC as a likely mechanism underlying the loss of H2Bub1. Finally, we demonstrated that H2Bub1 depletion promoted cell proliferation and clonogenicity in an endometriosis cell line. Collectively, our results indicate that H2Bub1 plays a tumor-suppressive role in CCOCs and that its loss contributes to disease progression.
巻・号 8(12)
公開日 2023-6-22
DOI 10.1172/jci.insight.164995
PII 164995
PMID 37345659
MeSH Carcinoma* Endometriosis* / genetics Female Histones / genetics Humans Ovarian Neoplasms* / genetics Peritoneal Neoplasms*
IF 6.205
リソース情報
ヒト・動物細胞 JHOC-5(RCB1520) JHOC-7(RCB1688) JHOC-9(RCB2226)