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

2009; Springer Nature; Volume: 17; Issue: 2 Linguagem: Inglês

10.1038/cdd.2009.117

1476-5403

Riccardo Spizzo, Milena S. Nicoloso, Laura Lupini, Yiling Lu, Julie A Fogarty, Simona Rossi, Barbara Zagatti, Muller Fabbri, Angelo Veronese, X Liu, Ramana V. Davuluri, Carlo M. Croce, Gordon B. Mills, Massimo Negrini, George A. Calin,

Circular RNAs in diseases

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.