Suppressive role exerted by microRNA-29b-1-5p in triple negative breast cancer through SPIN1 regulation

Renza Vento, Anna De Blasio, Daniela Carlisi, Riccardo Di Fiore, James Degaetano, Francesca Pentimalli, Christian Saliba, Shawn Baldacchino, Joseph Debono, Gordon Caruana-Dingli, Renza Vento, Giovanni Tesoriere, Antonio Giordano, Christian Scerri, Godfrey Grech, Rosa Drago Ferrante

Risultato della ricerca: Article

24 Citazioni (Scopus)

Abstract

MiR-29 family dysregulation occurs in various cancers including breast cancers. We investigated miR-29b-1 functional role in human triple negative breast cancer (TNBC) the most aggressive breast cancer subtype. We found that miR-29b-1-5p was downregulated in human TNBC tissues and cell lines. To assess whether miR-29b-1-5p correlated with TNBC regenerative potential, we evaluated cancer stem cell enrichment in our TNBC cell lines, and found that only MDA-MB-231 and BT-20 produced primary, secondary and tertiary mammospheres, which were progressively enriched in OCT4, NANOG and SOX2 stemness genes. MiR-29b-1-5p expression inversely correlated with mammosphere stemness potential, and miR-29b-1 ectopic overexpression decreased TNBC cell growth, self-renewal, migration, invasiveness and paclitaxel resistance repressing WNT/βcatenin and AKT signaling pathways and stemness regulators. We identified SPINDLIN1 (SPIN1) among predicted miR-29b-1-5p targets. Consistently, SPIN1 was overexpressed in most TNBC tissues and cell lines and negatively correlated with miR-29b-1-5p. Target site inhibition showed that SPIN1 seems to be directly controlled by miR-29b-1-5p. Silencing SPIN1 mirrored the effects triggered by miR-29b-1 overexpression, whereas SPIN1 rescue by SPIN1miScript protector, determined the reversal of the molecular effects produced by the mimic-miR-29b-1-5p. Overall, we show that miR-29b-1 deregulation impacts on multiple oncogenic features of TNBC cells and their renewal potential, acting, at least partly, through SPIN1, and suggest that both these factors should be evaluated as new possible therapeutic targets against TNBC.
Lingua originaleEnglish
pagine (da-a)28939-28958
Numero di pagine20
RivistaOncotarget
Stato di pubblicazionePublished - 2017

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Triple Negative Breast Neoplasms
MicroRNAs
Breast Neoplasms
Cell Line
Catenins
Neoplastic Stem Cells
Paclitaxel
Down-Regulation

All Science Journal Classification (ASJC) codes

  • Oncology

Cita questo

Suppressive role exerted by microRNA-29b-1-5p in triple negative breast cancer through SPIN1 regulation. / Vento, Renza; De Blasio, Anna; Carlisi, Daniela; Di Fiore, Riccardo; Degaetano, James; Pentimalli, Francesca; Saliba, Christian; Baldacchino, Shawn; Debono, Joseph; Caruana-Dingli, Gordon; Vento, Renza; Tesoriere, Giovanni; Giordano, Antonio; Scerri, Christian; Grech, Godfrey; Drago Ferrante, Rosa.

In: Oncotarget, 2017, pag. 28939-28958.

Risultato della ricerca: Article

Vento, R, De Blasio, A, Carlisi, D, Di Fiore, R, Degaetano, J, Pentimalli, F, Saliba, C, Baldacchino, S, Debono, J, Caruana-Dingli, G, Vento, R, Tesoriere, G, Giordano, A, Scerri, C, Grech, G & Drago Ferrante, R 2017, 'Suppressive role exerted by microRNA-29b-1-5p in triple negative breast cancer through SPIN1 regulation', Oncotarget, pagg. 28939-28958.
Vento, Renza ; De Blasio, Anna ; Carlisi, Daniela ; Di Fiore, Riccardo ; Degaetano, James ; Pentimalli, Francesca ; Saliba, Christian ; Baldacchino, Shawn ; Debono, Joseph ; Caruana-Dingli, Gordon ; Vento, Renza ; Tesoriere, Giovanni ; Giordano, Antonio ; Scerri, Christian ; Grech, Godfrey ; Drago Ferrante, Rosa. / Suppressive role exerted by microRNA-29b-1-5p in triple negative breast cancer through SPIN1 regulation. In: Oncotarget. 2017 ; pagg. 28939-28958.
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title = "Suppressive role exerted by microRNA-29b-1-5p in triple negative breast cancer through SPIN1 regulation",
abstract = "MiR-29 family dysregulation occurs in various cancers including breast cancers. We investigated miR-29b-1 functional role in human triple negative breast cancer (TNBC) the most aggressive breast cancer subtype. We found that miR-29b-1-5p was downregulated in human TNBC tissues and cell lines. To assess whether miR-29b-1-5p correlated with TNBC regenerative potential, we evaluated cancer stem cell enrichment in our TNBC cell lines, and found that only MDA-MB-231 and BT-20 produced primary, secondary and tertiary mammospheres, which were progressively enriched in OCT4, NANOG and SOX2 stemness genes. MiR-29b-1-5p expression inversely correlated with mammosphere stemness potential, and miR-29b-1 ectopic overexpression decreased TNBC cell growth, self-renewal, migration, invasiveness and paclitaxel resistance repressing WNT/βcatenin and AKT signaling pathways and stemness regulators. We identified SPINDLIN1 (SPIN1) among predicted miR-29b-1-5p targets. Consistently, SPIN1 was overexpressed in most TNBC tissues and cell lines and negatively correlated with miR-29b-1-5p. Target site inhibition showed that SPIN1 seems to be directly controlled by miR-29b-1-5p. Silencing SPIN1 mirrored the effects triggered by miR-29b-1 overexpression, whereas SPIN1 rescue by SPIN1miScript protector, determined the reversal of the molecular effects produced by the mimic-miR-29b-1-5p. Overall, we show that miR-29b-1 deregulation impacts on multiple oncogenic features of TNBC cells and their renewal potential, acting, at least partly, through SPIN1, and suggest that both these factors should be evaluated as new possible therapeutic targets against TNBC.",
keywords = "MiR-29b-1, SPIN1, Wnt/β-catenin and Akt signaling pathways, cancer stem cells, triple-negative breast cancer",
author = "Renza Vento and {De Blasio}, Anna and Daniela Carlisi and {Di Fiore}, Riccardo and James Degaetano and Francesca Pentimalli and Christian Saliba and Shawn Baldacchino and Joseph Debono and Gordon Caruana-Dingli and Renza Vento and Giovanni Tesoriere and Antonio Giordano and Christian Scerri and Godfrey Grech and {Drago Ferrante}, Rosa",
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TY - JOUR

T1 - Suppressive role exerted by microRNA-29b-1-5p in triple negative breast cancer through SPIN1 regulation

AU - Vento, Renza

AU - De Blasio, Anna

AU - Carlisi, Daniela

AU - Di Fiore, Riccardo

AU - Degaetano, James

AU - Pentimalli, Francesca

AU - Saliba, Christian

AU - Baldacchino, Shawn

AU - Debono, Joseph

AU - Caruana-Dingli, Gordon

AU - Vento, Renza

AU - Tesoriere, Giovanni

AU - Giordano, Antonio

AU - Scerri, Christian

AU - Grech, Godfrey

AU - Drago Ferrante, Rosa

PY - 2017

Y1 - 2017

N2 - MiR-29 family dysregulation occurs in various cancers including breast cancers. We investigated miR-29b-1 functional role in human triple negative breast cancer (TNBC) the most aggressive breast cancer subtype. We found that miR-29b-1-5p was downregulated in human TNBC tissues and cell lines. To assess whether miR-29b-1-5p correlated with TNBC regenerative potential, we evaluated cancer stem cell enrichment in our TNBC cell lines, and found that only MDA-MB-231 and BT-20 produced primary, secondary and tertiary mammospheres, which were progressively enriched in OCT4, NANOG and SOX2 stemness genes. MiR-29b-1-5p expression inversely correlated with mammosphere stemness potential, and miR-29b-1 ectopic overexpression decreased TNBC cell growth, self-renewal, migration, invasiveness and paclitaxel resistance repressing WNT/βcatenin and AKT signaling pathways and stemness regulators. We identified SPINDLIN1 (SPIN1) among predicted miR-29b-1-5p targets. Consistently, SPIN1 was overexpressed in most TNBC tissues and cell lines and negatively correlated with miR-29b-1-5p. Target site inhibition showed that SPIN1 seems to be directly controlled by miR-29b-1-5p. Silencing SPIN1 mirrored the effects triggered by miR-29b-1 overexpression, whereas SPIN1 rescue by SPIN1miScript protector, determined the reversal of the molecular effects produced by the mimic-miR-29b-1-5p. Overall, we show that miR-29b-1 deregulation impacts on multiple oncogenic features of TNBC cells and their renewal potential, acting, at least partly, through SPIN1, and suggest that both these factors should be evaluated as new possible therapeutic targets against TNBC.

AB - MiR-29 family dysregulation occurs in various cancers including breast cancers. We investigated miR-29b-1 functional role in human triple negative breast cancer (TNBC) the most aggressive breast cancer subtype. We found that miR-29b-1-5p was downregulated in human TNBC tissues and cell lines. To assess whether miR-29b-1-5p correlated with TNBC regenerative potential, we evaluated cancer stem cell enrichment in our TNBC cell lines, and found that only MDA-MB-231 and BT-20 produced primary, secondary and tertiary mammospheres, which were progressively enriched in OCT4, NANOG and SOX2 stemness genes. MiR-29b-1-5p expression inversely correlated with mammosphere stemness potential, and miR-29b-1 ectopic overexpression decreased TNBC cell growth, self-renewal, migration, invasiveness and paclitaxel resistance repressing WNT/βcatenin and AKT signaling pathways and stemness regulators. We identified SPINDLIN1 (SPIN1) among predicted miR-29b-1-5p targets. Consistently, SPIN1 was overexpressed in most TNBC tissues and cell lines and negatively correlated with miR-29b-1-5p. Target site inhibition showed that SPIN1 seems to be directly controlled by miR-29b-1-5p. Silencing SPIN1 mirrored the effects triggered by miR-29b-1 overexpression, whereas SPIN1 rescue by SPIN1miScript protector, determined the reversal of the molecular effects produced by the mimic-miR-29b-1-5p. Overall, we show that miR-29b-1 deregulation impacts on multiple oncogenic features of TNBC cells and their renewal potential, acting, at least partly, through SPIN1, and suggest that both these factors should be evaluated as new possible therapeutic targets against TNBC.

KW - MiR-29b-1

KW - SPIN1

KW - Wnt/β-catenin and Akt signaling pathways

KW - cancer stem cells

KW - triple-negative breast cancer

UR - http://hdl.handle.net/10447/226025

M3 - Article

SP - 28939

EP - 28958

JO - Oncotarget

JF - Oncotarget

SN - 1949-2553

ER -