miR-145 participates with TP53 in a death-promoting regulatory loop and targets estrogen receptor-[alpha] in human breast cancer cells

• Published in: Cell death and differentiation Vol. 17; no. 2; pp. 246 - 254
• Main Authors: 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, G, Negrini, M, Calin, G A
• Format: Journal Article
• Language: English
• Published: Rome Nature Publishing Group 01.02.2010
• Subjects: Apoptosis; Biology; Breast cancer; Cell death; Cell growth; Cyclin-dependent kinases; Estrogens; Gene expression; Kinases; Medical research; MicroRNAs; Proteins; Stem cells; Tumors; United States > US; Italy
• ISSN: 1350-9047; 1476-5403
• DOI: 10.1038/cdd.2009.117

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-alpha (ER-alpha) 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-alpha. Moreover, our findings support a view that miR-145 re-expression therapy could be mainly envisioned in the specific group of patients with ER-alpha-positive and/or TP53 wild-type tumors.