MiR-129-5p is required for histone deacetylase inhibitor-induced cell death in thyroid cancer cells

被引:83
作者
Brest, Patrick [2 ]
Lassalle, Sandra [2 ,3 ,4 ]
Hofman, Veronique [2 ,3 ,4 ]
Bordone, Olivier [3 ]
Tanga, Virginie Gavric [3 ]
Bonnetaud, Christelle [3 ]
Moreilhon, Chimene [5 ,6 ]
Rios, Geraldine [6 ]
Santini, Jose [7 ,8 ]
Barbry, Pascal [6 ]
Svanborg, Catharina [9 ]
Mograbi, Baharia [2 ]
Mari, Bernard [6 ]
Hofman, Paul [1 ,2 ,3 ,4 ]
机构
[1] Univ Nice Sophia Antipolis, IRCAN, F-06107 Nice, France
[2] INSERM ERI 21, EA4319, Nice, France
[3] Hop Louis Pasteur, Ctr Hosp Univ Nice, Ctr Ressource Biol INSERM, F-06002 Nice, France
[4] Hop Louis Pasteur, Ctr Hosp Univ Nice, Lab Pathol Clin & Expt, F-06002 Nice, France
[5] Hop Louis Pasteur, Ctr Hosp Univ Nice, Lab Oncohematol, F-06002 Nice, France
[6] CNRS UMR 6097, Inst Pharmacol Mol & Cellulaire, Valbonne, France
[7] Hop Louis Pasteur, Ctr Hosp Univ Nice, Dept Otorhinolaryngol, F-06002 Nice, France
[8] Ctr Antoine Lacassagne, F-06054 Nice, France
[9] Lund Univ, Inst Lab Med, Dept Microbiol Immunol & Glycobiol, Lund, Sweden
基金
瑞典研究理事会;
关键词
VALPROIC ACID; CYCLE ARREST; IN-VITRO; APOPTOSIS; MICRORNAS; CARCINOMA; EXPRESSION; PROMOTE; LINE;
D O I
10.1530/ERC-10-0257
中图分类号
R73 [肿瘤学];
学科分类号
100214 [肿瘤学];
摘要
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 a-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. Endocrine-Related Cancer (2011) 18 711-719
引用
收藏
页码:711 / 719
页数:9
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