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Review
, 11 (10)

Epigenetic Drugs for Cancer and microRNAs: A Focus on Histone Deacetylase Inhibitors

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Review

Epigenetic Drugs for Cancer and microRNAs: A Focus on Histone Deacetylase Inhibitors

Pierre Autin et al. Cancers (Basel).

Abstract

Over recent decades, it has become clear that epigenetic abnormalities are involved in the hallmarks of cancer. Histone modifications, such as acetylation, play a crucial role in cancer development and progression, by regulating gene expression, such as for oncogenes or tumor suppressor genes. Therefore, histone deacetylase inhibitors (HDACi) have recently shown efficacy against both hematological and solid cancers. Designed to target histone deacetylases (HDAC), these drugs can modify the expression pattern of numerous genes including those coding for micro-RNAs (miRNA). miRNAs are small non-coding RNAs that regulate gene expression by targeting messenger RNA. Current research has found that miRNAs from a tumor can be investigated in the tumor itself, as well as in patient body fluids. In this review, we summarized current knowledge about HDAC and HDACi in several cancers, and described their impact on miRNA expression. We discuss briefly how circulating miRNAs may be used as biomarkers of HDACi response and used to investigate response to treatment.

Keywords: HDAC inhibitors; cancer; exosome; microRNA.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The main cellular processes affected in cancer cells by HDACi treatments. The decrease of histone acetylation by HDACi leads to the modification of the expression of several genes implicated in oncogenic properties of cancer cells. From top left to bottom right, HDACi reduces angiogenesis and tumor growth, HDACi improves treatments by inhibiting DNA repair, HDACi induces cell cycle arrest and stimulates apoptosis.
Figure 2
Figure 2
miRNAs modulated by HDACi treatments in cancer. HDACi upregulate TS-miR and downregulate oncomiR to inhibit proliferation and metastasis and to favor apoptosis.
Figure 3
Figure 3
miRNA biogenesis pathway. miRNA is transcribed in the nucleus and then cleaved numerous times to conduct to a mature single strand miRNA included in the RISC complex. miRNA may regulate gene expression in the cell but also in other cells by their encapsulation in microvesicles such as exosomes. miRNA may also be disseminated through the bloodstream. MVB: endosomal MultiVesicular bodies, RISC: RNA-induced silencing complex.

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