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; G. Mills; M. Negrini; G. A. Calin

doi:10.1038/cdd.2009.117

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, G. Mills, M. Negrini, G. A. Calin

Preventive Medicine

Research output: Contribution to journal › Article › peer-review

228 Scopus citations

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 language	English (US)
Pages (from-to)	246-254
Number of pages	9
Journal	Cell Death and Differentiation
Volume	17
Issue number	2
DOIs	https://doi.org/10.1038/cdd.2009.117
State	Published - Feb 2010

Funding

Acknowledgements. We thank Izabela Fokt (MD Anderson Cancer Center) for Adriamycin synthesis, Deepa Sampath (MD Anderson Cancer Center) for PUMA antibody and the Powis laboratory for the use of a luciferase plate reader. We thank Donald Norwood from the MD Anderson Scientific Publication Department for editing the paper. GAC is supported by The University of Texas MD Anderson Cancer Center Research Trust, The University of Texas System Regents Research Scholar Award and the Ladjevardian Regents Research Scholar Fund. This study was funded also by an Institutional Research Grant and the National Institutes of Health Cancer Center Support (Core) Grant (New Faculty Award) to GAC, and by the Associazione Italiana per la Ricerca sul Cancro and Fondazione Cariplo Progetto NOBEL (to MN).

Keywords

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

ASJC Scopus subject areas

Molecular Biology
Cell Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/cdd.2009.117

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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. (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, 17(2), 246-254. https://doi.org/10.1038/cdd.2009.117

@article{9be945d1f80a47d181c5f5a629df7f71,

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

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.",

keywords = "Apoptosis, Cell proliferation, ER-a, Human BC, MiR-145, TP53",

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

note = "Funding Information: Acknowledgements. We thank Izabela Fokt (MD Anderson Cancer Center) for Adriamycin synthesis, Deepa Sampath (MD Anderson Cancer Center) for PUMA antibody and the Powis laboratory for the use of a luciferase plate reader. We thank Donald Norwood from the MD Anderson Scientific Publication Department for editing the paper. GAC is supported by The University of Texas MD Anderson Cancer Center Research Trust, The University of Texas System Regents Research Scholar Award and the Ladjevardian Regents Research Scholar Fund. This study was funded also by an Institutional Research Grant and the National Institutes of Health Cancer Center Support (Core) Grant (New Faculty Award) to GAC, and by the Associazione Italiana per la Ricerca sul Cancro and Fondazione Cariplo Progetto NOBEL (to MN).",

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month = feb,

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pages = "246--254",

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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

TY - JOUR

T1 - MiR-145 participates with TP53 in a death-promoting regulatory loop and targets estrogen receptor-α in human breast cancer cells

AU - Spizzo, R.

AU - Nicoloso, M. S.

AU - Lupini, L.

AU - Lu, Y.

AU - Fogarty, J.

AU - Rossi, S.

AU - Zagatti, B.

AU - Fabbri, M.

AU - Veronese, A.

AU - Liu, X.

AU - Davuluri, R.

AU - Croce, C. M.

AU - Mills, G.

AU - Negrini, M.

AU - Calin, G. A.

N1 - Funding Information: Acknowledgements. We thank Izabela Fokt (MD Anderson Cancer Center) for Adriamycin synthesis, Deepa Sampath (MD Anderson Cancer Center) for PUMA antibody and the Powis laboratory for the use of a luciferase plate reader. We thank Donald Norwood from the MD Anderson Scientific Publication Department for editing the paper. GAC is supported by The University of Texas MD Anderson Cancer Center Research Trust, The University of Texas System Regents Research Scholar Award and the Ladjevardian Regents Research Scholar Fund. This study was funded also by an Institutional Research Grant and the National Institutes of Health Cancer Center Support (Core) Grant (New Faculty Award) to GAC, and by the Associazione Italiana per la Ricerca sul Cancro and Fondazione Cariplo Progetto NOBEL (to MN).

PY - 2010/2

Y1 - 2010/2

N2 - 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.

AB - 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.

KW - Apoptosis

KW - Cell proliferation

KW - ER-a

KW - Human BC

KW - MiR-145

KW - TP53

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DO - 10.1038/cdd.2009.117

M3 - Article

C2 - 19730444

AN - SCOPUS:74249123376

SN - 1350-9047

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SP - 246

EP - 254

JO - Cell Death and Differentiation

JF - Cell Death and Differentiation

IS - 2

ER -

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

Abstract

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

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