PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “decitabine”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed2026

Prognostic Role of Global DNA Methylation in Renal Cancer Reveals Decitabine Treatment Benefit.

BACKGROUND: Renal cancer presents a significant global health challenge due to its rising incidence and mortality rates. Often undetected in early stages, it complicates diagnosis and treatment. Current therapies face resistance and limited effectiveness, especially in advanced stages. The diverse subtypes of renal cancer highlight the need for new biomarkers and risk assessment tools for targeted treatments. OBJECTIVE: This study aims to assess the prognostic significance of global DNA methylation (GM) levels in renal cancer, identify new biomarkers, and evaluate the therapeutic potential of the DNA methyltransferase inhibitor decitabine. METHODS: Data on RNA sequencing, gene mutations, DNA methylation, and clinical outcomes were collected from TCGA and GEO databases. We calculated global DNA methylation scores (GMS) and categorized patients into high, intermediate, and low GMS groups. Survival analysis and genomic analyses were conducted to explore the relationships between GMS, clinical outcomes, and tumor characteristics. RESULTS: Higher GMS was identified as an independent prognostic factor associated with worse outcomes in renal cancer. Patients with elevated GMS showed increased mutations, copy number variations, and a more aggressive tumor phenotype. Treatment with decitabine was observed to reduce tumor hypermethylation and downregulate cell cycle pathway activity, indicating potential therapeutic benefits. CONCLUSION: Global DNA methylation plays a significant role in renal cancer prognosis. GMS may serve as valuable biomarkers for prognosis and personalized treatment strategies. Decitabine shows potential efficacy for high GMS patients, particularly through its impact on cell cycle regulation, underscoring the importance of personalized approaches in cancer treatment.

Humans↗
PubMed2026

Epigenetic Reactivation of TNFRSF19 Suppresses Mitophagy and Sensitizes Triple-Negative Breast Cancer to Doxorubicin.

Doxorubicin remains an important component of chemotherapy for triple-negative breast cancer (TNBC), yet chemoresistance severely limits its clinical efficacy. Here, we identify Tumor necrosis factor receptor superfamily member 19 (TNFRSF19) as an epigenetically silenced gene that critically regulates doxorubicin response. Integrative analyses of The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and clinical cohorts reveal that high TNFRSF19 expression predicts superior pathological complete response and improved survival in doxorubicin-treated TNBC patients. Mechanistically, TNFRSF19 binds the kinase domain of TGFBR1 via its intracellular domain, disrupting TGFBR1-SMAD3 complex formation and thereby inhibiting SMAD3 phosphorylation, nuclear translocation, and transcriptional activation of PTEN-induced putative kinase 1 (PINK1). This suppresses PINK1/Parkin-mediated mitophagy, contributing to mitochondrial dysfunction, reactive oxygen species (ROS) accumulation, and amplified DNA damage upon doxorubicin treatment. Notably, TNFRSF19 is downregulated in TNBC due to DNA hypermethylation, and decitabine restores its expression via promoter demethylation, thereby enhancing the therapeutic efficacy of doxorubicin in vitro and in vivo. Collectively, these findings establish TNFRSF19 as a critical epigenetic regulator of mitophagy, highlighting its potential as a predictive biomarker for doxorubicin response and a therapeutic target for sensitizing TNBC to doxorubicin.

DNA methylation↗
PubMed2026

Targeting TP53 in triple-negative breast cancer: Molecular pathogenesis, therapeutic implications, and emerging pharmacological strategies.

Triple-negative breast cancer (TNBC) remains a highly aggressive and therapeutically challenging subtype, defined by the absence of oestrogen, progesterone, and HER2 expression. Tumour Protein 53 (TP53) mutations represent the most frequent genetic alteration, occurring in over 80% of cases and driving tumour initiation, progression, and therapeutic resistance. Mutant p53 proteins not only lose canonical tumour-suppressive functions but also often acquire gain-of-function (GOF) oncogenic properties that promote metastasis, genomic instability, and resistance to mechanisms like ferroptosis. This review examines the biological role of TP53 in TNBC pathogenesis and evaluates emerging pharmacological strategies aimed at targeting these vulnerabilities. Key approaches include the pharmacological reactivation of mutant p53 using small molecules such as APR-246, COTI-2, and the mutation-specific reactivator rezatapopt (PC14586), which has shown significant clinical tumour reduction in Y220C-mutant patients. Other strategies involve targeted protein degradation, the exploitation of synthetic lethal interactions (e.g., Chk1 or Aurora kinase B inhibition), and the use of natural products like cryptolepine or piperine derivatives. Recent clinical evidence further highlights the potential of combining epigenetic agents like decitabine with chemotherapy in TP53-mutant populations. Integrating TP53 mutation status into biomarker-driven treatment paradigms is a pivotal step toward achieving precision oncology and improving clinical outcomes for patients with TNBC.

Precision oncology↗
PubMed2026

Targeting DNA Methylation: New Paradigms and the Advent of Gene-Selective Tools.

DNA methylation can function as a toxic alkylation reaction exploited by chemotherapeutic agents to induce cancer cell death. However, finely tuned DNA methylation plays a fundamental role in cellular physiology, particularly in the epigenetic regulation of gene expression. Once thought to act solely as a repressor of gene transcription, its functional role has since been elucidated as genomic locus-specific and deeply connected with other epigenetic factors. Following the clinical approval of DNA methyltransferase inhibitors, such as Azacitidine and Decitabine, for the treatment of hematological malignancies, considerable efforts have been devoted to developing pharmacological tools that modulate epigenetic DNA methylation. However, the lack of gene selectivity in these agents limits their therapeutic efficacy and increases off-target toxicity. Moreover, the non-gene-selective nature of current DNA methylation-targeting molecules fails to meet the standards required to discern the nuanced roles of DNA methylation across diverse pathophysiological contexts and genomic loci, particularly in an era where next-generation sequencing and omics technologies enable high-resolution epigenetic analyses. In this review, we examine the mechanisms and roles of DNA methylation in epigenetic regulation, evaluate the current landscape of DNA methylation modulators, from traditional DNMT inhibitors to cutting-edge CRISPR-dCas9 fusion systems and protein-protein interaction disruptors, and discuss their clinical relevance. Finally, we emphasize the need for precise, locus-specific tools to advance both cancer research and therapeutic strategies.

Humans↗
PubMed2025

Effect of extracellular vesicles in remodeling the tumor microenvironment by DNMT1 downregulation for enhanced cancer immunotherapy.

BACKGROUND: The efficacy of immunotherapy is often hindered by the suppression of immune responses via the tumor microenvironment (TME). The presence of cancer cells forces other proximal non-cancerous cells to support tumor growth and persistence. A clear example of this cancerous-to-non-cancerous communication is represented by the accumulation of myeloid-derived suppressor cells (MDSCs) within the TME. Several studies have convergently shown that the overexpression of DNA-methyl-transferase-1 (DNMT1) in these cells results in protection from necroptosis and enhanced accumulation in vivo. Conversely, targeting DNMT1 through hypo-methylating agents has shown promising therapeutic potential by not only reducing the levels of MDSCs but also enhancing cancer immunogenicity and the efficacy of immune checkpoint inhibitors (ICI). METHODS: Murine 4T1 (triple-negative breast cancer (TNBC)) and CT26 (colon carcinoma) cell lines were cultured under standard conditions and used to generate tumor models in BALB/c mice. An oncolytic adenovirus expressing a DNMT1-targeting short hairpin RNA (OAd.shDNMT1) was engineered and validated for DNMT1 knockdown and genome-wide methylation reduction. Small extracellular vesicles (sEVs) were isolated from virus-infected cancer cells and characterized for RNA content and uptake by MDSCs. MDSC differentiation and suppressive function were assessed in vitro using flow cytometry and co-culture assays with murine splenocytes. In vivo, tumor-bearing mice received intratumoral OAd.shDNMT1, systemic decitabine, or immune checkpoint inhibitors (anti-Programmed cell Death protein-1), and tumor growth, immune infiltration, and systemic MDSC levels were evaluated. RESULTS: In this study, we report that, by using virally infected TNBC murine cells as a source for shDNMT1-loaded sEVs, OAd.shDNMT1 successfully reduced MDSC levels in vitro and in vivo. Furthermore, the co-administration with ICI resulted in a significant tumor growth reduction in mice bearing poorly immunogenic TNBC 4T1 cells. Also, our treatment promoted antitumor immunity, prolonged survival, and complete tumor eradication in modestly immunogenic colon CT26 cancer cells. CONCLUSION: This multifaceted strategy, based on OV-mediated immune stimulation and reduction of MDSC levels via sEVs, may improve clinical outcomes and the success of immuno-based regimens for patients facing MDSC-rich and highly aggressive cancer subtypes.

Animals↗
PubMed1992

Potent inhibitors for the deamination of cytosine arabinoside and 5-aza-2'-deoxycytidine by human cytidine deaminase.

Deamination of the nucleoside analogues ARA-C and 5-AZA-CdR by CR deaminase results in a loss of antileukemic activity. To prevent the inactivation of these analogues, inhibitors of CR deaminase may prove to be useful agents. In the present study we investigated the effects of the deaminase inhibitors Zebularine, 5-F-Zebularine, and diazepinone riboside on the deamination of CR, ARA-C, and 5-AZA-CdR using highly purified human CR deaminase (EC 3.5.4.5). These inhibitors produced a competitive type of inhibition with each substrate, the potency of which followed the patterns diazepinone riboside greater than 5-F-Zebularine and THU greater than Zebularine. 5-AZA-CdR was more sensitive than ARA-C to the inhibition produced by these deaminase inhibitors. The inhibition constants for diazepinone riboside lay in the range of 5-15 nM, suggesting that this inhibitor could be an excellent candidate for use in combination chemotherapy with either ARA-C or 5-AZA-CdR in patients with leukemia.

Antineoplastic Agents↗
PubMed1992

Studies on the mechanism of the synergistic interaction between 2'-deoxy-5-azacytidine and cisplatin.

2'-Deoxy-5-azacytidine (5-aza-CdR) and cisplatin interact to produce synergistic cytotoxicity against many human tumor cell lines. Preliminary experiments designed to explore the mechanism of this synergy suggested a poor correlation between synergy and the degree of genomic hypomethylation measured following exposure to 5-aza-CdR. Subsequent studies using plasmid DNA suggested that rather than DNA hypomethylation, incorporation of 5-aza-CdR into DNA mediated increased cisplatin binding to DNA and could therefore be essential to the synergistic interaction between these two agents. In this series of experiments, we evaluated the degree of synergy with cisplatin produced against two human melanoma cell lines by two additional antimetabolites that were chosen on the basis of their biochemical properties. In addition, we investigated the synergy between 5-aza-CdR and cisplatin in parental and 5-aza-CdR-resistant murine cell lines, which differed in their sensitivity to 5-aza-CdR and DNA methylation status but incorporated similar amounts of 5-aza-CdR into DNA when exposed to this antimetabolite. In the studies testing additional antimetabolites, cytosine arabinoside, which is incorporated into DNA but does not hypomethylate it, produced synergy with cisplatin that was similar or superior to that obtained using 5-aza-CdR. With 3-deaza-adenosine, which is not incorporated into DNA but produces DNA hypomethylation through inhibition of S-adenosylhomocysteine hydrolase, a primarily antagonistic interaction was observed in the two cell lines studied. In the 5-aza-CdR-sensitive and -resistant cell lines, a very similar synergistic interaction was documented for 5-aza-CdR and cisplatin despite the significant difference observed in DNA methylation levels. Taken as a whole, these data suggest that DNA hypomethylation was not critical to the synergistic cytotoxicity produced by 5-aza-CdR and cisplatin. This finding suggests additional strategies that could further modulate this interaction.

Animals↗
PubMed1992

Induction of gene amplification by 5-aza-2'-deoxycytidine.

Treatment of Syrian hamster kidney cells with the demethylating agent 5-aza-2'-deoxycytidine (azadC) increased both the frequency and the rate of gene amplification appreciably. AzadC caused substantial DNA demethylation, which is likely to be responsible. The magnitude of the increases depended on the concentrations of both azadC and the drug used for selection. A transient stress response is not responsible since the increases were not dependent on cytotoxicity and were still apparent after several weeks. We discuss mechanisms by which azadC treatment may induce amplification by rendering DNA more prone to this process or by increasing the transcription of genes whose protein products stimulate amplification.

Animals↗
PubMed1992

Cytotoxicity of 5-aza-2'-deoxycytidine in a mammalian cell system.

After the addition of 5-aza-2'-deoxycytidine, a potent inhibitor of DNA methylation and S-phase-specific cytotoxic agent, metaphase chromosomes of Chinese hamster ovary (CHO) cells exhibited a highly decondensed and extended morphology (numerous "fragile sites") at the first mitotic division. However, when a lethal dose of this drug was added in early G1 phase to cells synchronised by mitotic selection, the majority subsequently divided at the same time as an untreated control cell population with few division abnormalities and with few of the more usual types of chromosome aberrations such as gaps, breaks and exchanges. The drug-treated cells also entered and completed the second S-phase without significant delay and it was only at the second mitosis after addition of 5-azadeoxycytidine that cells showed delays in entering mitosis and significant increases in abnormal divisions concomitant with a modest increase in chromosome aberrations. If cells in a tumour behave similarly, the tumour mass would be expected to double before any reduction in tumour burden could be expected to occur.

Animals↗
PubMed1992

Template-directed interference footprinting of cytosine contacts in a protein-DNA complex: potent interference by 5-aza-2'-deoxycytidine.

In the template-directed interference (TDI) footprinting method (Hayashibara & Verdine, 1990), analogs of the naturally occurring DNA bases are incorporated into DNA enzymatically and assayed for interference of sequence-specific binding by a protein. Here we extend this method to include analysis of contacts of amino acid residues to the major groove surface of cytosine residues (TDI-C footprinting). The base analog 5-aza-2'-deoxycytidine, in which the hydrophobic 5-CH of cytosine is replaced by a hydrophilic aza nitrogen, was incorporated into DNA via the corresponding 5'-triphosphate. The analog was found to base pair with guanine during polymerization, resulting in substitution of 2'-deoxycytidine residues. TDI-C footprints of the lambda repressor-OL1 operator complex revealed apparent contacts to the cytosines at operator positions 7 and 8. Inspection of the high-resolution X-ray crystal structure of the lambda-OL1 complex (Clarke et al., 1992; Beamer & Pabo, 1992) revealed that C8 makes a hydrogen binding contact with the Lys3; C7, on the other hand, makes a previously unnoticed hydrophobic contact with the alkane side chain of Lys3. In only the consensus operator half-site was cytosine interference observed, suggesting that the nonconsensus arm binds DNA very differently if at all. The N-terminal arm represents the archetypal case of a sequence-specific peptide-DNA complex characterized at high resolution; thus, the present studies suggest strategies for design and screening of DNA binding peptides. The finding that 5-aza-2'-deoxycytidine inhibits sequence-specific DNA binding proteins may suggest an alternative rationale for the biological activities of this and related azapyrimidine nucleosides.

Antineoplastic Agents↗
PubMed1992

Down-regulation of a member of the S100 gene family in mammary carcinoma cells and reexpression by azadeoxycytidine treatment.

A cDNA clone, designated CaN19 (originally called clone 19), isolated by subtractive hybridization, contains sequences that are preferentially expressed in normal mammary epithelial cells but not in breast tumor cells. Comparison of its deduced amino acid sequence with sequences in the GenBank data base revealed similarity with the S100 protein family, a group of small Ca(2+)-binding modulator proteins involved in cell cycle progression and cell differentiation. CaN19 expression is down-regulated in normal cells by A23187, a calcium ionophore, suggesting that its regulation is calcium-dependent. We have assigned CaN19 to human chromosome 1q21-q24, a region containing four other S100-related genes. In contrast to CaN19 mRNA expression, most members of the S100 protein family are activated or overexpressed in tumor cells. Synchronization experiments by growth-factor deprivation demonstrated a biphasic induction of CaN19 expression in normal cells, approximately 2-fold in early G1 phase and another 2- to 3-fold at the G1/S boundary. Exposure of mammary tumor cells to 5-aza-2'-deoxycytidine, an inhibitor of DNA methylation, reactivated the expression of CaN19 mRNA.

Amino Acid Sequence↗
PubMed1992

Progressive stages of "transdifferentiation" from epidermal to mesenchymal phenotype induced by MyoD1 transfection, 5-aza-2'-deoxycytidine treatment, and selection for reduced cell attachment in the human keratinocyte line HaCaT.

The ability of the myogenic determination gene (MyoD1) to convert differentiating human keratinocytes (HaCaT cell-line) to the myogenic pathway and the effect of MyoD1 on the epidermal phenotype was studied in culture and in surface transplants on nude mice. MyoD1 transfection induced the synthesis of myosin, desmin, and vimentin without substantially altering the epidermal differentiation properties (morphology, keratin profile) in vitro nor epidermal morphogenesis (formation of a complex stratified squamous epithelium) in surface transplants, demonstrating the stability of the keratinocyte phenotype. 5-Aza-CdR treatment of these MyoD1-transfected cells had little effect on the cultured cells but a morphologically unstructured epithelium was formed with no indications of typical cell layers including cornification. Since prevention of epidermal strata in transplants was not accompanied by blocked epidermal differentiation markers (keratins K1 and K10, involucrin, and filaggrin), the dissociation of morphogenesis and expression of these markers argues for independently controlled processes. A subpopulation of less adhesive cells, isolated from the 5-aza-CdR treated MyoD1-transfectants, had lost most epithelial characteristics in culture (epidermal keratins, desmosomal proteins, and surface-glycoprotein Gp90) and had shifted to a mesenchymal/myogenic phenotype (fibroblastic morphology, transactivation of Myf3 and myogenin, expression of myosin, desmin, vimentin, and Gp130). Moreover, the cells had lost the ability to stratify and remained as a monolayer of flat elongated cells in transplants. These subsequent changes from a fully differentiated keratinocyte to a mesenchymal/myogenic phenotype strongly argue for a complex "transdifferentiation" process which occurred in the original monoclonal human epidermal HaCaT cells.

Animals↗
PubMed1992

Production of thyroid tumours in mice by demethylating agents.

Previous studies on thyroid tumorigenesis in rodents have explored the role of oncogene mutation in tumour development. However, many mutagens are also known to decrease DNA methylation, another factor known to be important in the regulation of gene expression. We report the results of a small study to examine whether the demethylating agents 5-azacytidine and 5-aza-2-deoxycytidine could promote radiation- or goitrogen-induced tumorigenesis in the mouse, and whether they could potentiate the effect of a combined radiation and goitrogen regime. Three single doses of either 5-azacytidine or 5-aza-2-deoxycytidine increased the frequency of lesions in the goitrogen-treated animals; one of these lesions was a metastasising carcinoma. Thyroid carcinomas are very rare in mice in the absence of mutagen treatment, and metastasis is particularly unusual. There was no significant difference, at the dosages used, between the number of tumours induced by demethylating agents and those induced by a mutagen (radiation) in goitrogen-treated animals. Unlike goitrogens, demethylating agents did not promote radiation-induced tumorigenesis, and they did not produce any significant potentiation of the conventional regime of radiation and goitrogen at the dosages used. This study suggests that the role of non-genotoxic factors, such as agents affecting patterns of DNA methylation, warrants consideration in thyroid tumorigenesis.

Animals↗
PubMed1992

Effects of 5-aza-2'-deoxycytidine and interferon-alpha on differentiation and oncogene expression in HL-60 myeloid leukemic cells.

The antineoplastic effects of 5-aza-2'-deoxycytidine (5-AZA-CdR) and interferon-alpha (IFN-alpha) on human HL-60 myeloid leukemic cells were investigated. 5-AZA-CdR and IFN-alpha in combination produced a greater inhibition of DNA synthesis and cell growth than either agent alone. The co-treatment produced a synergistic reduction in the clonogenicity of the HL-60 leukemic cells. In addition, this combination also produced a greater reduction in mRNA expression for c-myc than each agent alone. This antileukemic action produced by 5-AZA-CdR and IFN-alpha in combination correlated with the increase in induction of differentiation of the HL-60 leukemic cells. These results suggest that 5-AZA-CdR and IFN-alpha in combination produces an enhancement of their antineoplastic action on HL-60 human myeloid leukemic cells.

Antineoplastic Agents↗
PubMed2025

Dual EZH1/2 inhibition enhances DNMT inhibitor efficacy in colon cancer through targeting H3K27me1.

Our recent work showed that low-dose DNMT inhibitor (DNMTi) treatment sensitizes colon cancer cells to EZH2 inhibitors (EZH2i), synergistically upregulating tumor suppressor genes (TSGs) and transposable elements through activation of the calcium-calcineurin-NFAT signaling pathway. A key observation was that EZH2i displayed variable sensitivities in combination therapy, which could not be explained solely by loss of lysine 27 trimethylation on histone H3 (H3K27me3), the most commonly studied EZH2 product. This led us to perform a comprehensive pharmacologic screen of Polycomb Repressive Complex 2 (PRC2) antagonists. Here, we show that compounds targeting both EZH2 and its interchangeable catalytic subunit, EZH1, achieved superior TSG re-expression when combined with DNMTi. Integrative proteomic and epigenomic analyses revealed that EZH1/2 inhibitors reduce all three H3K27 methylation states, whereas EZH2-selective inhibitors preserve EZH1-dependent H3K27me1 at deeply Polycomb-repressed genomic regions. Notably, H3K27me1 loss coincided with deposition of p300/CBP-dependent lysine 27 acetylation on histone H3 (H3K27ac), which proved essential for TSG re-expression. Paradoxically, blocking p300/CBP activity further enhanced the growth-inhibitory effects of combined DNMT and EZH1/2 inhibition. Mechanistically, we show that EZH1/2 inhibition redistributes p300/CBP activity, reducing H3K27ac from oncogenic loci and redirecting it to bivalent regions that enable TSG re-expression. Collectively, these findings reveal a coordinated role for EZH1-dependent H3K27me1 and DNA methylation in sustaining oncogenic transcriptional programs and provide strong rationale for advancing dual EZH1/2 inhibitors for combination epigenetic cancer therapy.

DNA methylation↗
PubMed1992

Hemimethylation and hypersensitivity are early events in transcriptional reactivation of human inactive X-linked genes in a hamster x human somatic cell hybrid.

Reactivation of the hypoxanthine phosphoribosyltransferase (HPRT) gene on an inactive human X chromosome in a somatic cell hybrid was analyzed following exposure to 5-aza-2'-deoxycytidine. Hemimethylation and chromatin hypersensitivity in the 5' CpG island appeared by 6 h after exposure and continued to increase for 24 h in an exponentially growing cell culture. These results imply that the conformation of inactive chromatin requires a symmetrically methylated 5' G+C-rich promoter region. In addition, quantitative analysis of the time course patterns suggest that chromatin sensitivity changes may depend on strand-specific demethylation. Symmetrically demethylated DNA was first detected at 24 h and continued to increase until 48 h. HPRT mRNA was first detected at 24 h and increased in a biphasic pattern until 48 h. These results suggest that hemimethylation permits nuclease attack but not transcription factor binding, which requires symmetrically demethylated DNA. We also show that in G1-arrested cells, 5-aza-2'-deoxycytidine has no effect on methylation, chromatin conformation, or transcription. We conclude that reactivation of the HPRT gene present on the inactive X chromosome of a somatic cell hybrid involves the initial events of DNA hemimethylation and chromatin hypersensitivity at the 5' CpG island, followed by symmetrical demethylation and transcriptional reactivation.

Animals↗
PubMed2024

Differential expression and regulation of ADAD1, DMRTC2, PRSS54, SYCE1, SYCP1, TEX101, TEX48, and TMPRSS12 gene profiles in colon cancer tissues and their in vitro response to epigenetic drugs.

Colon cancer (CC) is a significant cause of death worldwide, particularly in Saudi Arabia. To increase the accuracy of diagnosis and treatment, it is important to discover new specific biomarkers for CC. The main objectives of this research are to identify potential specific biomarkers for the early diagnosis of CC by analyzing the expressions of eight cancer testis (CT) genes, as well as to analyze how epigenetic mechanisms control the expression of these genes in CC cell lines. Tissue samples were collected from 15 male patients with CC tissues and matched NC tissues for gene expression analysis. The expression levels of specific CT genes, including ADAD1, DMRTC2, PRSS54, SYCE1, SYCP1, TEX101, TEX48, and TMPRSS12, were assessed using quantitative techniques. To validate the gene expression patterns, we used publicly available CC statistics. To investigate the effect of inhibition of DNA methylation and histone deacetylation on CT gene expression, in vitro experiments were performed using HCT116 and Caco-2 cell lines. There was no detected expression of the genes neither in the patient samples nor in NC tissues, except for TEX48, which exhibited upregulation in CC samples compared to NC tissues in online datasets. Notably, CT genes showed expression in testis samples. In vitro, experiments demonstrated significant enhancement in mRNA expression levels of ADAD1, DMRTC2, PRSS54, SYCE1, SYCP1, TEX101, TEX48, and TMPRSS12 following treatment with 5-aza-2'-deoxycytidine and trichostatin A in HCT116 and Caco-2 cell lines. Epigenetic treatments modify the expression of CT genes, indicating that these genes can potentially be used as biomarkers for CC. The importance of conducting further research to understand and target epigenetic mechanisms to improve CC treatment cannot be overemphasized.

Humans↗