Epigenetic alternations concern heritable yet reversible changes in histone or DNA modifications that regulate gene activity beyond the underlying sequence. Epigenetic dysregulation is often linked to human disease, notably cancer. With the development of various drugs targeting epigenetic regulators, epigenetic-targeted therapy has been applied in the treatment of hematological malignancies and has exhibited viable therapeutic potential for solid tumors in preclinical and clinical trials. In this review, we summarize the aberrant functions of enzymes in DNA methylation, histone acetylation and histone methylation during tumor progression and highlight the development of inhibitors of or drugs targeted at epigenetic enzymes.

/pdf/targeting-epigenetic-regulators-for-cancer-therapy-2zwakpbmfn.pdf

Targeting epigenetic regulators for cancer therapy: mechanisms and advances in clinical trials.

https://www.cell.com/trends/genetics/pdf/S0168-9525(14)00069-9.pdf

Sirtuins: Guardians of Mammalian Healthspan

SIRT6, a member of the Sirtuin family of NAD+-dependent enzymes, has established roles in chromatin signaling and genome maintenance. Through these functions, SIRT6 protects against aging-associated pathologies including metabolic disease and cancer, and can promote longevity in mice. Research from the past few years revealed that SIRT6 is a complex enzyme with multiple substrates and catalytic activities, and uncovered novel SIRT6 functions in the maintenance of organismal health span. Here, we review these new discoveries and models of SIRT6 biology in four areas: heterochromatin stabilization and silencing; stem cell biology; cancer initiation and progression; and regulation of metabolic homeostasis. We discuss the possible implications of these findings for therapeutic interventions in aging and aging-related disease processes.

SIRT6: Novel Mechanisms and Links to Aging and Disease.

Mammalian sirtuins have emerged in recent years as critical modulators of multiple biological processes, regulating cellular metabolism, DNA repair, gene expression, and mitochondrial biology. As s...

https://journals.physiology.org/doi/pdf/10.1152/physrev.00030.2018

SIRT6, a Mammalian Deacylase with Multitasking Abilities.

The mammalian sirtuin family has attracted tremendous attention over the past few years as stress adaptors and post-translational modifier. They have involved in diverse cellular processes including DNA repair, energy metabolism, and tumorigenesis. Notably, genomic instability and metabolic reprogramming are two of characteristic hallmarks in cancer. In this review, we summarize current knowledge on the functions of sirtuins mainly regarding DNA repair and energy metabolism, and further discuss the implication of sirtuins in cancer specifically by regulating genome integrity and cancer-related metabolism.

https://link.springer.com/content/pdf/10.1186%2Fs13046-016-0461-5.pdf

Sirtuins in metabolism, DNA repair and cancer

SI RT6 is an important histone modifying protein that regulates DNA repair, telomere maintenance, energy me-tabolism, and target gene expression. Recently SIRT6 has been identiﬁ ed as a tumor suppressor and is down-regulated in certain cancer types, but not in other can-cers. From deposited gene proﬁ ling studies we found that SIRT6 was overexpressed in prostate tumors, compared with normal or paratumor prostate tissues. Tissue micro-array studies conﬁ rmed the higher levels of SIRT6 in both prostate tumor tissues and prostate cancer cells than in their normal counterparts. Knockdown of SIRT6 in human prostate cancer cells led to sub-G

/pdf/inhibition-of-sirt6-in-prostate-cancer-reduces-cell-41re5r9mfc.pdf

Inhibition of SIRT6 in prostate cancer reduces cell viability and increases sensitivity to chemotherapeutics ESEARCH ARTICLE R

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Inhibition of SIRT6 in prostate cancer reduces cell viability and increases sensitivity to chemotherapeutics ESEARCH ARTICLE R