Histone deacetylase inhibitors promote ATP2A3 gene expression in hepatocellular carcinoma cells: p300 as a transcriptional regulator

Hernández‐Oliveras, Andrés; Izquierdo-Torres, Eduardo; Meneses-Morales, Iván; Rodrı́guez, Gabriela; Zarain‐Herzberg, Ángel; Santiago‐García, Juan

doi:10.1016/j.biocel.2019.05.014

Cited by 15 publications

(10 citation statements)

References 32 publications

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“…Another study in breast cancer indicated the involvement of SERCA3 in early stage lobular dysplasia, with low expression levels at more advanced stages of lobular tumorigenesis [ 25 ]. In invasive breast carcinoma, SERCA3 expression levels are significantly decreased compared with that in normal patients, indicating that SERCA3 expression is inversely associated with tumor differentiation and the degree of aggressiveness/malignancy of ductal carcinoma [ 18 , 24 , 25 , 26 , 27 , 28 ].…”

Section: Introductionmentioning

confidence: 99%

Altered SERCA Expression in Breast Cancer

et al. 2021

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Background and Objectives: Calcium (Ca2+) signaling is critical for the normal functioning of various cellular activities. However, abnormal changes in cellular Ca2+ can contribute to pathological conditions, including various types of cancer. The maintenance of intracellular Ca2+ levels is achieved through tightly regulated processes that help maintain Ca2+ homeostasis. Several types of regulatory proteins are involved in controlling intracellular Ca2+ levels, including the sarco/endoplasmic reticulum (SR/ER) Ca2+ ATPase pump (SERCA), which maintains Ca2+ levels released from the SR/ER. In total, three ATPase SR/ER Ca2+-transporting (ATP2A) 1-3 genes exist, which encode for several isoforms whose expression profiles are tissue-specific. Recently, it has become clear that abnormal SERCA expression and activity are associated with various types of cancer, including breast cancer. Breast carcinomas represent 40% of all cancer types that affect women, with a wide variety of pathological and clinical conditions. Results: The present study found significantly different SERCA specific-type expressions in a series of breast cancer cell lines. Moreover, bioinformatics analysis indicated that ATP2A1 and ATP2A3 expression was highly altered in patients with breast cancer. Methodology: Using cBioPortal breast cancer patient data, Kaplan–Meier plots demonstrated that high ATP2A1 and ATP2A3 expression was associated with reduced patient survival. Conclusion: Overall, the present data suggest that SERCA gene-specific expressioncan possibly be considered as a crucial target for the control of breast cancer development and progression.

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Section: Introductionmentioning

confidence: 99%

Altered SERCA Expression in Breast Cancer

et al. 2021

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“…Trichostatin A (TSA) is a potent and reversible inhibitor of histone deacetylase (HDAC), therefore acting as an epigenetic modifier by preventing the removal of acetyl groups from lysine residues on histone tails. TSA can be used to selectively promote gene transcription by maintaining chromatin histone H3K27 acetylation [ 45 ]. At E4.5, we administered the TSA or DMSO into the right mesonephric kidney where the early gonad originated and examined the expression levels of the situs-biased genes 24 h later (Additional file 13 : Fig.…”

Section: Resultsmentioning

confidence: 99%

H3K27ac chromatin acetylation and gene expression analysis reveal sex- and situs-related differences in developing chicken gonads

et al. 2022

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Background Birds exhibit a unique asymmetry in terms of gonad development. The female left gonad generates a functional ovary, whereas the right gonad regresses. In males, both left and right gonads would develop into testes. How is this left/right asymmetry established only in females but not in males remains unknown. The epigenetic regulation of gonadal developmental genes may contribute to this sex disparity. The modification of histone tails such as H3K27ac is tightly coupled to chromatin activation and gene expression. To explore whether H3K27ac marked chromatin activation is involved in the asymmetric development of avian gonads, we probed genome-wide H3K27ac occupancy in left and right gonads from both sexes and related chromatin activity profile to the expression of gonadal genes. Furthermore, we validated the effect of chromatin activity on asymmetric gonadal development by manipulating the chromatin histone acetylation levels. Methods The undifferentiated gonads from both sides of each sex were collected and subjected to RNA-Seq and H3K27ac ChIP-Seq experiments. Integrated analysis of gene expression and active chromatin regions were performed to identify the sex- and situs-specific regulation and expression of gonadal genes. The histone deacetylase inhibitor trichostatin A (TSA) was applied to the undifferentiated female right gonads to assess the effect of chromatin activation on gonadal gene expression and cell proliferation. Results Even before sex differentiation, the gonads already show divergent gene expression between different sexes and between left/right sides in females. The sex-specific H3K27ac chromatin distributions coincide with the higher expression of male/female specification genes in each sex. Unexpectedly, the H3K27ac marked chromatin activation show a dramatic difference between left and right gonads in both sexes, although the left/right asymmetric gonadal development was observed only in females but not in males. In females, the side-specific H3K27ac occupancy instructs the differential expression of developmental genes between the pair of gonads and contributes to the development of left but not right gonad. However, in males, the left/right discrepancy of H3K27ac chromatin distribution does not drive the side-biased gene expression or gonad development. The TSA-induced retention of chromatin acetylation causes up-regulation of ovarian developmental genes and increases cell proliferation in the female right gonad. Conclusions We revealed that left/right asymmetry in H3K27ac marked chromatin activation exists in both sexes, but this discrepancy gives rise to asymmetric gonadal development only in females. Other mechanisms overriding the chromatin activation would control the symmetric development of male gonads in chicken.

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“…Moreover, trichostatin A (TSA), an antifungal antibiotic with pan-HDACi activity is effective in several tumor models at the nanomolar level. TSA inhibits HDAC activity [69], downregulates HDAC1 expression [75], increases histone H4 [69] and estrogen receptor (ER) acetylation in breast cancer cell lines [76], increases histone H3 lysine 9 and lysine 27 acetylation [76] and upregulates p21, p27 and p57 expression in colon cancer cell lines [75] Additionally, in PCa, TSA increases histone H4 lysine 16 acetylation, particularly in CRPC cell lines [73], and affects p53 acetylation [49]. In addition, TSA presents nonepigenetic effects, including decreased cell proliferation [68,74], increased cell death [72,75] with an increase in active caspase-3 levels [71], increased hypoxic responses [74], downregulation of cyclin D1 gene expression [71], cell cycle arrest at G 1 phase, increased expression of Bax gene and downregulated Bcl-2 gene expression and decreased phosphorylation of Akt and ERK proteins [70].…”

Section: Hdac Inhibitorsmentioning

confidence: 99%

Repurposing Old Drugs into New Epigenetic Inhibitors: Promising Candidates for Cancer Treatment?

et al. 2020

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Epigenetic alterations, as a cancer hallmark, are associated with cancer initiation, progression and aggressiveness. Considering, however, that these alterations are reversible, drugs that target epigenetic machinery may have an inhibitory effect upon cancer treatment. The traditional drug discovery pathway is time-consuming and expensive, and thus, new and more effective strategies are required. Drug Repurposing (DR) comprises the discovery of a new medical indication for a drug that is approved for another indication, which has been recalled, that was not accepted or failed to prove efficacy. DR presents several advantages, mainly reduced resources, absence of the initial target discovery process and the reduced time necessary for the drug to be commercially available. There are numerous old drugs that are under study as repurposed epigenetic inhibitors which have demonstrated promising results in in vitro tumor models. Herein, we summarize the DR process and explore several repurposed drugs with different epigenetic targets that constitute promising candidates for cancer treatment, highlighting their mechanisms of action.

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Histone deacetylase inhibitors promote ATP2A3 gene expression in hepatocellular carcinoma cells: p300 as a transcriptional regulator

Cited by 15 publications

References 32 publications

Altered SERCA Expression in Breast Cancer

Altered SERCA Expression in Breast Cancer

H3K27ac chromatin acetylation and gene expression analysis reveal sex- and situs-related differences in developing chicken gonads

Repurposing Old Drugs into New Epigenetic Inhibitors: Promising Candidates for Cancer Treatment?

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