Histone H1.3 suppresses H19 noncoding RNA expression and cell growth of ovarian cancer cells

Magdalena Medrzycki, Yunzhe Zhang, Weijia Zhang, Kaixiang Cao, Chenyi Pan, Nathalie Lailler, John F. McDonald, Eric E. Bouhassira, Yuhong Fan

Research output: Contribution to journalArticle

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Abstract

Ovarian cancer is a deadly gynecologic malignancy for which novel biomarkers and therapeutic targets are imperative for improving survival. Previous studies have suggested the expression pattern of linker histone variants as potential biomarkers for ovarian cancer. To investigate the role of histone H1 in ovarian cancer cells, we characterize individual H1 variants and overexpress one of the major somatic H1 variants, H1.3, in the OVCAR-3 epithelial ovarian cancer cell line.We find that overexpression of H1.3 decreases the growth rate and colony formation of OVCAR-3 cells. We identify histone H1.3 as a specific repressor for the noncoding oncogene H19. Overexpression of H1.3 suppresses H19 expression, and knockdown of H1.3 increases its expression in multiple ovarian epithelial cancer cell lines. Furthermore, we demonstrate that histone H1.3 overexpression leads to increased occupancy of H1.3 at the H19 regulator region encompassing the imprinting control region (ICR), concomitant with increased DNA methylation and reduced occupancy of the insulator protein CTCF at the ICR. Finally, we demonstrate that H1.3 overexpression and H19 knockdown synergistically decrease the growth rate of ovarian cancer cells. Our findings suggest that H1.3 dramatically inhibits H19 expression, which contributes to the suppression of epithelial ovarian carcinogenesis.

Original languageEnglish (US)
Pages (from-to)6463-6473
Number of pages11
JournalCancer Research
Volume74
Issue number22
DOIs
StatePublished - Nov 15 2014

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Untranslated RNA
Ovarian Neoplasms
Histones
Growth
Biomarkers
Cell Line
DNA Methylation
Oncogenes
Carcinogenesis
Epithelial Cells
H19 long non-coding RNA
Neoplasms
Ovarian epithelial cancer
Therapeutics

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Medrzycki, M., Zhang, Y., Zhang, W., Cao, K., Pan, C., Lailler, N., ... Fan, Y. (2014). Histone H1.3 suppresses H19 noncoding RNA expression and cell growth of ovarian cancer cells. Cancer Research, 74(22), 6463-6473. https://doi.org/10.1158/0008-5472.CAN-13-2922

Histone H1.3 suppresses H19 noncoding RNA expression and cell growth of ovarian cancer cells. / Medrzycki, Magdalena; Zhang, Yunzhe; Zhang, Weijia; Cao, Kaixiang; Pan, Chenyi; Lailler, Nathalie; McDonald, John F.; Bouhassira, Eric E.; Fan, Yuhong.

In: Cancer Research, Vol. 74, No. 22, 15.11.2014, p. 6463-6473.

Research output: Contribution to journalArticle

Medrzycki, M, Zhang, Y, Zhang, W, Cao, K, Pan, C, Lailler, N, McDonald, JF, Bouhassira, EE & Fan, Y 2014, 'Histone H1.3 suppresses H19 noncoding RNA expression and cell growth of ovarian cancer cells', Cancer Research, vol. 74, no. 22, pp. 6463-6473. https://doi.org/10.1158/0008-5472.CAN-13-2922
Medrzycki, Magdalena ; Zhang, Yunzhe ; Zhang, Weijia ; Cao, Kaixiang ; Pan, Chenyi ; Lailler, Nathalie ; McDonald, John F. ; Bouhassira, Eric E. ; Fan, Yuhong. / Histone H1.3 suppresses H19 noncoding RNA expression and cell growth of ovarian cancer cells. In: Cancer Research. 2014 ; Vol. 74, No. 22. pp. 6463-6473.
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