HDAC1 (Histone Deacetylase 1)

Murine and human MDSC models treated with Entinostat revealed that the long non-coding RNA Malat1 downregulates pSTAT3 and decreases MDSC-mediated suppression of T cell proliferation...Collectively, our findings provide a multi-pronged mechanism of HDAC inhibition in MDSCs that inform the development of future rational combination therapies. HDAC1 inhibition in MDSCs increases Malat1 , decreases pSTAT3, induces apoptosis/cell cycle arrest, and decreases suppression of T cells.

Our findings reveal an epigenetic-Hippo-immunomodulatory axis in osteosarcoma that also extends to other sarcomas, providing a rationale for incorporating epigenetic preconditioning with immunotherapy to improve patient outcomes and pointing towards novel biomarkers for treatment guidance.

Exploration of the upstream mechanism revealed that hsa_circSFPQ_008, which was derived from the SFPQ parental gene, recruits HDAC1 to modify H3K27Ac of the SFPQ promoter and regulates its expression. This study reveals a novel regulatory mechanism by which SFPQ is involved in platinum resistance of ovarian cancer, providing a new theoretical basis for the individualized and precise treatment of ovarian cancer.

Moreover, DAM upregulated the expression of SCFA receptors GPR41 and GPR43, enhanced H3K9ac and suppressed HDAC1 expression, suggesting epigenetic modulation of Wnt/β-catenin signaling. Collectively, DAM attenuates liver fibrosis by modulating the SCFAs-Wnt/β-catenin signaling axis, providing new insights into gut-liver axis regulation and supporting DAM as a promising antifibrotic candidate.

Together, our findings establish a robust link between cell cycle progression and histone modification dynamics, highlighting the necessity of maintaining balanced PTM levels under varying proliferative states. These insights have broad implications for our understanding of development, aging, and tumor growth.

Leveraging scaffold hopping and structural optimization strategies, we developed fifteen indole-based derivatives utilizing vorinostat (SAHA) and entinostat as lead compounds. Mechanistic investigations of representative hydroxamate and benzamide derivatives corroborated their marked antiproliferative effects in HCT-116 cancer cells and manifested a favorable safety profile against the normal fibroblasts (WI-38). Altogether, these findings underscore the therapeutic potential of the identified potent compounds for combating cancer via HDAC1/6 inhibition.

Our results suggest the existence of a newly identified mechanism underlying the regulation of BCLAF1 splicing orchestrated, at least in part, by the interplay between HDAC1 and DNMT3A, and directly correlated with the healthy or cancerous state of hematopoietic cells. Our findings shed light on a novel regulatory axis in AML and highlight the potential of epidrugs to restore normal splicing patterns, paving the way for innovative therapies.

The RT-PCR analysis showed that the melatonin modulates the alterations in HDAC1, 2, 6, and 9 and DNMT1, DNMT3A and DNMT3B with respect to the control. The MS-PCR results signify one of the possible ways of action of melatonin on DL cells.

In vivo, Entinostat suppressed tumor growth and consistently modulated the HDAC1/p53/AMPK/mTOR pathway. In conclusion, Entinostat exerts potent anti-tumor activity in SCLC by simultaneously inducing apoptosis and autophagy through epigenetic modulation of p53 via HDAC1 inhibition and subsequent regulation of the AMPK/mTOR axis.

Glabridin reduces inflammation by modulating colonic macrophage polarization, while emodin inhibits ferroptosis via gut microbiota remodeling mediated by Nrf2. This review explores oxidative stress, lipid peroxidation, ferroptosis, apoptosis, inflammation, autophagy, epigenetics, and gut microbiota in DIC, alongside promising pharmacological strategies to mitigate its effects.