ARID1A and CEBPα cooperatively inhibit UCA1 transcription in breast cancer

Xiao Guo, Yin Zhang, Anand Mayakonda, Vikas Madan, Ling Wen Ding, Le Hang Lin, Saadiya Zia, Sigal Gery, Jeffrey Tyner, Wu Zhou, Dong Yin, De Chen Lin, H. Phillip Koeffler

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

As one of the primary members of SWI/SNF chromatin remodeling complexes, ARID1A contains frequent loss-of-function mutations in many types of cancers. However, the molecular mechanisms underlying ARID1A deficiency in cancer biology remain to be investigated. Using breast cancer as a model, we report that silencing ARID1A significantly increased cellular proliferation and migration. Mechanistically, primarily functioning as a transcriptional repressor, loss of ARID1A profoundly alters histone modifications and the transcriptome. Notably, ARID1A inhibited the expression of a long non-coding RNA, UCA1, by regulating chromatin access of the transcription factor CEBPα. Restoration experiments showed that UCA1 mediates the functions of ARID1A that induces loss of cellular proliferation and migration. Together, our findings characterize ARID1A as a key tumor-suppressor gene in breast cancer through cooperation with CEBPα, and loss-of-function mutations of ARID1A activates UCA1.

Original languageEnglish (US)
Pages (from-to)1-13
Number of pages13
JournalOncogene
DOIs
StateAccepted/In press - Jul 6 2018

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Histone Code
Cell Proliferation
Long Noncoding RNA
Breast Neoplasms
Mutation
Chromatin Assembly and Disassembly
Tumor Suppressor Genes
Transcriptome
Chromatin
Neoplasms
Transcription Factors

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Guo, X., Zhang, Y., Mayakonda, A., Madan, V., Ding, L. W., Lin, L. H., ... Koeffler, H. P. (Accepted/In press). ARID1A and CEBPα cooperatively inhibit UCA1 transcription in breast cancer. Oncogene, 1-13. https://doi.org/10.1038/s41388-018-0371-4

ARID1A and CEBPα cooperatively inhibit UCA1 transcription in breast cancer. / Guo, Xiao; Zhang, Yin; Mayakonda, Anand; Madan, Vikas; Ding, Ling Wen; Lin, Le Hang; Zia, Saadiya; Gery, Sigal; Tyner, Jeffrey; Zhou, Wu; Yin, Dong; Lin, De Chen; Koeffler, H. Phillip.

In: Oncogene, 06.07.2018, p. 1-13.

Research output: Contribution to journalArticle

Guo, X, Zhang, Y, Mayakonda, A, Madan, V, Ding, LW, Lin, LH, Zia, S, Gery, S, Tyner, J, Zhou, W, Yin, D, Lin, DC & Koeffler, HP 2018, 'ARID1A and CEBPα cooperatively inhibit UCA1 transcription in breast cancer', Oncogene, pp. 1-13. https://doi.org/10.1038/s41388-018-0371-4
Guo, Xiao ; Zhang, Yin ; Mayakonda, Anand ; Madan, Vikas ; Ding, Ling Wen ; Lin, Le Hang ; Zia, Saadiya ; Gery, Sigal ; Tyner, Jeffrey ; Zhou, Wu ; Yin, Dong ; Lin, De Chen ; Koeffler, H. Phillip. / ARID1A and CEBPα cooperatively inhibit UCA1 transcription in breast cancer. In: Oncogene. 2018 ; pp. 1-13.
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