Abstract
Cell migration plays major roles in human renal cancer-related death, but the molecular mechanisms remain unclear. Valproic acid (VPA) is a broad-spectrum inhibitor of class I and II histone deacetylases and shows great anticancer activity in a variety of human cancers. In this study, we found that VPA significantly inhibited cell migration but not proliferation of human renal cancer ACHN cells. Mechanistic studies found that VPA significantly inhibited the expression of HIF-1α. Knockdown of HIF-1α could obviously inhibited cell migration, while over-expression of HIF-1α markedly rescued the inhibition of VPA on cell migration. Further studies found that knockdown of HDAC2 completely mimicked the effects of VPA on HIF-1α and cell migration, and over-expression of HIF-1α could also rescue the effects of HDAC2 knockdown on cell migration. Collectively, these results indicated that the potential of specific inhibition of HDAC2 by small molecular chemicals may lead to future therapeutic agents in human renal cancer treatment.
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Abbreviations
- RCC:
-
Renal cell carcinoma
- ccRCC:
-
Clear cell renal cell carcinoma
- VPA:
-
Valproic acid
- PCR:
-
Polymerase chain reaction
- 786-O:
-
Cultivated cells of human renal cell cancer
- ACHN:
-
Human kidney adenocarcinoma cell line
- HDAC:
-
Histone deacetylase
- HIF-1α:
-
Hypoxia-inducible factor-1 alpha
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This work was partially supported by grants from the National Natural Science Foundation of China (Nos. 81270831 and 81000311).
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The authors declared no potential conflicts of interests with respect to the authorship and/or publication of this article.
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Feng-qiang Yang, Min Liu and Feng-ping Yang have contributed equally to this work.
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Yang, Fq., Liu, M., Yang, Fp. et al. VPA inhibits renal cancer cell migration by targeting HDAC2 and down-regulating HIF-1α. Mol Biol Rep 41, 1511–1518 (2014). https://doi.org/10.1007/s11033-013-2996-2
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DOI: https://doi.org/10.1007/s11033-013-2996-2