MiR-145 participates with TP53 in a death-promoting regulatory loop and targets estrogen receptor-α in human breast cancer cells

R. Spizzo, M. S. Nicoloso, L. Lupini, Y. Lu, J. Fogarty, S. Rossi, B. Zagatti, M. Fabbri, A. Veronese, X. Liu, R. Davuluri, C. M. Croce, Gordon Mills, M. Negrini, G. A. Calin

Research output: Contribution to journalArticle

180 Citations (Scopus)

Abstract

Understanding the consequences of miR-145 reintroduction in human breast cancer (BC) could reveal its tumor-suppressive functions and may disclose new aspects of BC biology. Therefore, we characterized the effects of miR-145 re-expression in BC cell lines by using proliferation and apoptosis assays. As a result, we found that miR-145 exhibited a pro-apoptotic effect, which is dependent on TP53 activation, and that TP53 activation can, in turn, stimulate miR-145 expression, thus establishing a death-promoting loop between miR-145 and TP53. We also found that miR-145 can downregulate estrogen receptor-α (ER-α) protein expression through direct interaction with two complementary sites within its coding sequence. In conclusion, we described a tumor suppression function of miR-145 in BC cell lines, and we linked miR-145 to TP53 and ER-α. Moreover, our findings support a view that miR-145 re-expression therapy could be mainly envisioned in the specific group of patients with ER-α-positive and/or TP53 wild-type tumors.

Original languageEnglish (US)
Pages (from-to)246-254
Number of pages9
JournalCell Death and Differentiation
Volume17
Issue number2
DOIs
StatePublished - Feb 1 2010
Externally publishedYes

Fingerprint

Estrogen Receptors
Breast Neoplasms
Cell Line
Neoplasms
Down-Regulation
Apoptosis
Therapeutics

Keywords

  • Apoptosis
  • Cell proliferation
  • ER-a
  • Human BC
  • MiR-145
  • TP53

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

MiR-145 participates with TP53 in a death-promoting regulatory loop and targets estrogen receptor-α in human breast cancer cells. / Spizzo, R.; Nicoloso, M. S.; Lupini, L.; Lu, Y.; Fogarty, J.; Rossi, S.; Zagatti, B.; Fabbri, M.; Veronese, A.; Liu, X.; Davuluri, R.; Croce, C. M.; Mills, Gordon; Negrini, M.; Calin, G. A.

In: Cell Death and Differentiation, Vol. 17, No. 2, 01.02.2010, p. 246-254.

Research output: Contribution to journalArticle

Spizzo, R, Nicoloso, MS, Lupini, L, Lu, Y, Fogarty, J, Rossi, S, Zagatti, B, Fabbri, M, Veronese, A, Liu, X, Davuluri, R, Croce, CM, Mills, G, Negrini, M & Calin, GA 2010, 'MiR-145 participates with TP53 in a death-promoting regulatory loop and targets estrogen receptor-α in human breast cancer cells', Cell Death and Differentiation, vol. 17, no. 2, pp. 246-254. https://doi.org/10.1038/cdd.2009.117
Spizzo, R. ; Nicoloso, M. S. ; Lupini, L. ; Lu, Y. ; Fogarty, J. ; Rossi, S. ; Zagatti, B. ; Fabbri, M. ; Veronese, A. ; Liu, X. ; Davuluri, R. ; Croce, C. M. ; Mills, Gordon ; Negrini, M. ; Calin, G. A. / MiR-145 participates with TP53 in a death-promoting regulatory loop and targets estrogen receptor-α in human breast cancer cells. In: Cell Death and Differentiation. 2010 ; Vol. 17, No. 2. pp. 246-254.
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