title: MiR-129-5p is required for histone deacetylase inhibitor-induced cell death in thyroid cancer cells.
abstract: The molecular mechanism responsible for the antitumor activity of histone deacetylase inhibitors (HDACi) remains elusive. As HDACi have been described to alter miRNA expression, the aim of this study was to characterize HDACi-induced miRNAs and to determine their functional importance in the induction of cell death alone or in combination with other cancer drugs. Two HDACi, trichostatin A and vorinostat, induced miR-129-5p overexpression, histone acetylation and cell death in BCPAP, TPC-1, 8505C, and CAL62 cell lines and in primary cultures of papillary thyroid cancer (PTC) cells. In addition, miR-129-5p alone was sufficient to induce cell death and knockdown experiments showed that expression of this miRNA was required for HDACi-induced cell death. Moreover, miR-129-5p accentuated the anti-proliferative effects of other cancer drugs such as etoposide or human α-lactalbumin made lethal for tumor cells (HAMLET). Taken together, our data show that miR-129-5p is involved in the antitumor activity of HDACi and highlight a miRNA-driven cell death mechanism.
authors.affiliation: Nice, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Brest
authors.forename: Sandra
authors.initials: S
authors.lastname: Lassalle
authors.forename: Veronique
authors.initials: V
authors.lastname: Hofman
authors.forename: Olivier
authors.initials: O
authors.lastname: Bordone
authors.forename: Virginie
authors.initials: V
authors.lastname: Gavric Tanga
authors.forename: Christelle
authors.initials: C
authors.lastname: Bonnetaud
authors.forename: Chimene
authors.initials: C
authors.lastname: Moreilhon
authors.forename: Geraldine
authors.initials: G
authors.lastname: Rios
authors.forename: José
authors.initials: J
authors.lastname: Santini
authors.forename: Pascal
authors.initials: P
authors.lastname: Barbry
authors.forename: Catharina
authors.initials: C
authors.lastname: Svanborg
authors.forename: Baharia
authors.initials: B
authors.lastname: Mograbi
authors.forename: Bernard
authors.initials: B
authors.lastname: Mari
authors.forename: Paul
authors.initials: P
authors.lastname: Hofman
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D002277:Carcinoma; D002291:Carcinoma, Papillary; D016923:Cell Death / Q000187:drug effects / Q000235:genetics; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000502:physiology; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006801:Humans; D007768:Lactalbumin / Q000494:pharmacology; D035683:MicroRNAs / Q000235:genetics / Q000502:physiology*; D046228:Microarray Analysis; D009829:Oleic Acids / Q000494:pharmacology; D061251:Primary Cell Culture; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000235:genetics / Q000473:pathology*; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; C506422:HAMLET complex, human; D056572:Histone Deacetylase Inhibitors; D035683:MicroRNAs; C541915:Mirn129 microRNA, human; D009829:Oleic Acids; D007768:Lactalbumin