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

2011 ◽  
Vol 18 (6) ◽  
pp. 711-719 ◽  
Author(s):  
Patrick Brest ◽  
Sandra Lassalle ◽  
Veronique Hofman ◽  
Olivier Bordone ◽  
Virginie Gavric Tanga ◽  
...  

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.

Oncotarget ◽  
2016 ◽  
Vol 7 (15) ◽  
pp. 19559-19574 ◽  
Author(s):  
Chiara Ciardiello ◽  
Maria Serena Roca ◽  
Alessia Noto ◽  
Francesca Bruzzese ◽  
Tania Moccia ◽  
...  

2020 ◽  
Vol 26 ◽  
Author(s):  
Eleftherios Spartalis ◽  
Konstantinos Kotrotsios ◽  
Dimosthenis Chrysikos ◽  
Michael Spartalis ◽  
Stavroula A. Paschou ◽  
...  

Background/Aim: Papillary Thyroid Cancer (PTC) is the most common type of endocrine malignancy. Although PTC has an excellent prognosis, recurrent or metastatic disease could affect patients survival. Recent studies show that Histone Deacetylase Inhibitors (HDACIs) might be promising anticancer agents against PTC. The aim of this review is to evaluate the role of HDACIs as an additional modality in PTC treatment and to depict the latest trends of current research on this field. Materials and Methods: This literature review was performed using the MEDLINE database. The search strategy included terms: “thyroid cancer”, “papillary”, “HDAC”, “histone”, and “deacetylase”. Results: Agents, such as Suberoyl Anilide Hydroxamic Acid, Trichostatin A, Valproic Acid, Sodium butyrate, Panobinostat, Belinostat, Romidepsin, CUDC907 and N-Hydroxy-7-(2-naphthylthio)-Hepanomide have shown promising anti-cancer effects on PTC cell lines but fail to trigger major response in clinical trials. Conclusion: HDACIs have no significant effect as monotherapy against PTC but further research needs to be conducted in order to investigate their potential effect when used as an additional modality.


Neoplasia ◽  
2007 ◽  
Vol 9 (6) ◽  
pp. 495-503 ◽  
Author(s):  
Chitra Subramanian ◽  
Jason A. Jarzembowski ◽  
Anthony W. Opipari ◽  
Valerie P. Castle ◽  
Roland P.S. Kwok

2012 ◽  
Vol 48 (3) ◽  
pp. 217-227 ◽  
Author(s):  
Cinzia Puppin ◽  
Nadia Passon ◽  
Jerome M Hershman ◽  
Sebastiano Filetti ◽  
Stefania Bulotta ◽  
...  

Histone deacetylase inhibitors (HDACi) have shown both anti-proliferative and redifferentiating effects in thyroid cancer cells. Also, they induce the expression of the sodium–iodide symporter gene (NIS(SLC5A5)), a crucial step for radioiodine treatment of thyroid malignancies. Here we investigated the effects of suberoylanilide hydroxamic acid (SAHA) and valproic acid (VPA) on BCPAP and FRO thyroid cancer cells, extending our analysis on the epigenetic mechanisms underlying theNISgene expression stimulation. In both cell lines we found a cooperative effect of the two compounds on either cell viability andNISgene expression, resulting in acquired/increased ability to uptake the radioiodine. Such effect was specific since it was not observed for expression of other genes or when SAHA was used in combination with trichostatin A. By using chromatin immunoprecipitation, we investigated epigenetic mechanisms underlying SAHA and VPA effects. Cooperation among the two HDACi occurred on H3 histone trimethylation at lysine 4 (H3K4me3) and not on histone acetylation. However, effects on H3K4me3 were detected only at the level of NIS Proximal Basal Promoter (NIS-PBP) in FRO cells and only at the level of NIS Upstream Enhancer (NIS-NUE) in BCPAP cells. Our data indicate that epigenetic changes are involved in the synergistic effects of VPA and SAHA onNISgene expression and that the cellular context modifies effects of HDACi in terms of H3K4me3 target sequence. Investigation of cooperation among different HDACi may provide clues for better defining their mechanism of action in view of their use in thyroid cancer treatment.


Sign in / Sign up

Export Citation Format

Share Document