MiR-129-5p is required for histone deacetylase inhibitor-induced cell death in thyroid cancer cells
MiR-129-5p is required for histone deacetylase inhibitor-induced cell death in thyroid cancer cells
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DOI：
10.1530/erc-10-0257
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发表时间：
2011-12-01
影响因子：
3.9
通讯作者：
Hofman, Paul
中科院分区：
文献类型：
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作者：
Brest, Patrick;Lassalle, Sandra;Hofman, Paul
组蛋白去乙酰化酶抑制剂（HDACi）的抗肿瘤活性的分子机制仍然难以捉摸。由于HDACi已被描述为改变miRNA表达，本研究的目的是表征HDACi诱导的miRNA，并确定其在单独或与其他癌症药物联合诱导细胞死亡中的功能重要性。在BCPAP、TPC-1、8505 C和CAL 62细胞系以及乳头状甲状腺癌（PTC）细胞的原代培养物中，两种HDACi（阿司他汀A和伏立诺他）诱导miR-129- 5 p过表达、组蛋白乙酰化和细胞死亡。此外，单独的miR-129- 5 p足以诱导细胞死亡，并且敲低实验表明，该miRNA的表达是HDACi诱导的细胞死亡所必需的。此外，miR-129- 5 p增强了其他癌症药物的抗增殖作用，例如使肿瘤细胞致死的依托泊苷或人α-乳白蛋白（哈姆雷特）。综上所述，我们的数据表明miR-129- 5 p参与HDACi的抗肿瘤活性，并突出了miRNA驱动的细胞死亡机制。内分泌相关癌症（2011）18 711-719
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