HMGA1a induces alternative splicing of estrogen receptor alpha in MCF-7 human breast cancer cells

Kenji Ohe, Shinsuke Miyajima, Ichiro Abe, Tomoko Tanaka, Yuriko Hamaguchi, Yoshihiro Harada, Yuta Horita, Yuki Beppu, Fumiaki Ito, Takafumi Yamasaki, Hiroki Terai, Masayoshi Mori, Yusuke Murata, Makito Tanabe, Kenji Ashida, Kunihisa Kobayashi, Munechika Enjoji, Toshihiko Yanase, Nobuhiro Harada, Toshiaki UtsumiAkila Mayeda

研究成果: Article

5 引用 (Scopus)

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The high-mobility group A protein 1a (HMGA1a) protein is known as an oncogene whose expression level in cancer tissue correlates with the malignant potential, and known as a component of senescence-related structures connecting it to tumor suppressor networks in fibroblasts. HMGA1 protein binds to DNA, but recent studies have shown it exerts novel functions through RNA-binding. Our previous studies have shown that sequence-specific RNA-binding of HMGA1a induces exon-skipping of Presenilin-2 exon 5 in sporadic Alzheimer disease. Here we show that HMGA1a induced exon-skipping of the estrogen receptor alpha (ERα) gene and increased ERα46 mRNA expression in MCF-7 breast cancer cells. An RNA-decoy of HMGA1a efficiently blocked this event and reduced ERα46 protein expression. Blockage of HMGA1a RNA-binding property consequently induced cell growth through reduced ERα46 expression in MCF-7 cells and increased sensitivity to tamoxifen in the tamoxifen-resistant cell line, MCF-7/TAMR1. Stable expression of an HMGA1a RNA-decoy in MCF-7 cells exhibited decreased ERα46 protein expression and increased estrogen-dependent tumor growth when these cells were implanted in nude mice. These results show HMGA1a is involved in alternative splicing of the ERα gene and related to estrogen-related growth as well as tamoxifen sensitivity in MCF-7 breast cancer cells.

元の言語English
ページ(範囲)21-26
ページ数6
ジャーナルJournal of Steroid Biochemistry and Molecular Biology
182
DOI
出版物ステータスPublished - 09-2018

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All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Endocrinology
  • Clinical Biochemistry
  • Cell Biology

これを引用

Ohe, K., Miyajima, S., Abe, I., Tanaka, T., Hamaguchi, Y., Harada, Y., Horita, Y., Beppu, Y., Ito, F., Yamasaki, T., Terai, H., Mori, M., Murata, Y., Tanabe, M., Ashida, K., Kobayashi, K., Enjoji, M., Yanase, T., Harada, N., ... Mayeda, A. (2018). HMGA1a induces alternative splicing of estrogen receptor alpha in MCF-7 human breast cancer cells. Journal of Steroid Biochemistry and Molecular Biology, 182, 21-26. https://doi.org/10.1016/j.jsbmb.2018.04.007