Synergistic effects of the combination of 5-Aza‑CdR and suberoylanilide hydroxamic acid on the anticancer property of pancreatic cancer

Han, Ting; Zhao, Meng; Hu, Hai; Jiao, Feng

doi:10.3892/or.2017.6059

Cited by 9 publications

(10 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Western blot analysis was conducted as previously described [ 11 ]. The primary antibodies were as follows: anti-AGO2 (1:1000), anti-ZEB1 (1:1000, Cell Signaling Technology, Beverly, MA, USA), and anti-β-Actin (1:2500, Santa Cruz Biotechnology, Santa Cruz, CA, USA).…”

Section: Methodsmentioning

confidence: 99%

A novel feedback loop between high MALAT-1 and low miR-200c-3p promotes cell migration and invasion in pancreatic ductal adenocarcinoma and is predictive of poor prognosis

et al. 2018

Self Cite

View full text Add to dashboard Cite

BackgroundIt was demonstrated that long non-coding RNAs occupied an important position in tumor pathogenesis and progression. We have previously found that the metastasis-associated lung adenocarcinoma transcript 1 (MALAT-1) promotes cell proliferation and metastases in pancreatic ductal adenocarcinoma (PDAC). The present study was aimed to discuss the underlying mechanisms.MethodsBioinformatics method was used to identify the miRNA target of MALAT-1. Expressions of relative genes were assessed by quantitative real-time PCR and western blotting, respectively. Sulforhodamine B assay and Transwell assay were employed to detect cell proliferation, migration and invasion, respectively. Moreover, RNA immunoprecipitation was performed to determine whether RNA-induced silencing complex contained MALAT-1 and its potential binding miRNA. Luciferase assays was used to confirm potential binding site.ResultsBioinformatics search predicted that miR-200c-3p was a direct target of MALAT-1. Further, we found a reciprocal suppression between MALAT-1 and miR-200c-3p expression. In terms of mechanisms, high MALAT-1 and low miR-200c-3p may form a novel feedback loop. On the one hand, MALAT-1 functioned as a competing endogenous RNA to suppress miR-200c-3p expression, leading to upregulation of ZEB1 expression. On the other hand, miR-200c-3p inhibited the level of MALAT-1 expression was in a way similar to miRNA-mediated downregulation of target genes. Clinical data further indicated that MALAT-1 and ZEB1 expression was negatively correlated with miR-200c-3p transcript level of PDAC tissues. There was a positive correlation between MALAT-1 and ZEB1 level. MALAT-1 (high)/miR-200c-3p (low) correlated with shorter overall survival of PDAC patients. Multivariate analysis revealed that both MALAT-1 and miR-200c-3p levels were independent prognostic factors.ConclusionOur findings firstly revealed a novel feedback loop between high MALAT-1 and low miR-200c-3p. Targeting the feedback loop between high MALAT-1 and low miR-200c-3p will be a therapeutic strategy for PDAC.Electronic supplementary materialThe online version of this article (10.1186/s12885-018-4954-9) contains supplementary material, which is available to authorized users.

show abstract

Section: Methodsmentioning

confidence: 99%

A novel feedback loop between high MALAT-1 and low miR-200c-3p promotes cell migration and invasion in pancreatic ductal adenocarcinoma and is predictive of poor prognosis

et al. 2018

Self Cite

View full text Add to dashboard Cite

show abstract

“…11–13 In this context, DNA hypomethylating agents, such as azacitidine and decitabine, have been used in the clinic setting for decades as anticancer therapy for several tumors. 14–16 Histone deacetylase inhibitors (HDACi) are also an emerging class of cancer therapies. 17–20 Moreover, several lysine methyltransferases and demethylases have been identified as promising targets for pharmacological intervention.…”

Section: Introductionmentioning

confidence: 99%

Thymoquinone-Induced Reactivation of Tumor Suppressor Genes in Cancer Cells Involves Epigenetic Mechanisms

et al. 2019

View full text Add to dashboard Cite

The epigenetic silencing of tumor suppressor genes (TSGs) is a common finding in several solid and hematological tumors involving various epigenetic readers and writers leading to enhanced cell proliferation and defective apoptosis. Thymoquinone (TQ), the major biologically active compound of black seed oil, has demonstrated anticancer activities in various tumors by targeting several pathways. However, its effects on the epigenetic code of cancer cells are largely unknown. In the present study, we performed RNA sequencing to investigate the anticancer mechanisms of TQ-treated T-cell acute lymphoblastic leukemia cell line (Jurkat cells) and examined gene expression using different tools. We found that many key epigenetic players, including ubiquitin-like containing plant homeodomain (PHD) and really interesting new gene (RING) finger domains 1 ( UHRF1), DNMT1,3A,3B, G9A, HDAC1,4,9, KDM1B , and KMT2A,B,C,D,E , were downregulated in TQ-treated Jurkat cells. Interestingly, several TSGs, such as DLC1, PPARG, ST7, FOXO6, TET2, CYP1B1, SALL4 , and DDIT3 , known to be epigenetically silenced in various tumors, including acute leukemia, were upregulated, along with the upregulation of several downstream pro-apoptotic genes, such as RASL11B, RASD1, GNG3, BAD , and BIK . Data obtained from RNA sequencing were confirmed using quantitative reverse transcription polymerase chain reaction (RT-qPCR) in Jurkat cells, as well as in a human breast cancer cell line (MDA-MB-468 cells). We found that the decrease in cell proliferation and in the expression of UHRF1, DNMT1, G9a , and HDAC1 genes in both cancer cell (Jurkat cells and MDA-MB-468 cells) lines depends on the TQ dose. Our results indicate that the use of TQ as an epigenetic drug represents a promising strategy for epigenetic therapy for both solid and blood tumors by targeting both DNA methylation and histone post-translational modifications.

show abstract

“…In-vitro studies have shown that 5-Aza-CdR, a DNA methyltransferase 1 (DNMT1) inhibitor, could induce cell death and apoptosis of pancreatic cancer cells by reactivation of RASSF1A and up-regulation of Bax genes (36). Han et al also observed the synergistic effects of the combination of 5-Aza-CdR and suberoylanilide hydroxamic acid on the anticancer property of PC (37). More inspiring, phase I/II clinical trials of DNMT1 inhibitors (azacitidine, decitabine and guadecitabine) in PC patients were currently underway, the inhibitors of which exhibited potential treatment outcomes (38).…”

Section: Discussionmentioning

confidence: 99%

Cpg Island Methylator Phenotype With Distinctly Different Prognosis And Molecular Features In Pancreatic Cancer Patient

Ning

Chen

et al. 2021

Preprint

View full text Add to dashboard Cite

BackgroundCpG island methylator phenotype (CIMP), featured with concurrent and widespread hypermethylation of a cluster of CpGs, has been reported to play an important role in carcinogenesis. Limited studies have investigated the CIMP in pancreatic cancer (PC). The aim of this study was to explore the CIMP in PC patients and its clinical-pathological and genomic characteristics. Methods:DNA methylation, somatic mutation, mRNA and corresponding clinical data of PC patients were downloaded from TCGA (184 patients) and ICGC (264 patients). Univariate and multivariate regression analysis were used to identify prognosis related CpGs. Consensus clustering analysis was used for identification of the CIMP in PC patients. ESTIMATE and CIBORORT were used for estimation of tumor microenvironment (TME) in PC patients.ResultsIn TCGA PC cohort, 22,450 differential CpGs, including 12,937 hypermethylated CpGs and 9,513 hypomethylated CpGs were identified between185 PC patients and 10 normal controls. Univariate and multivariate Cox analysis further screened out 72 OS related CpGs and three distinct CIMP groups with distinctly different prognosis and molecular features, including CIMP-L subgroup, CIMP-M subgroup and CIMP-H subgroup were identified based on unsupervised consensus clustering analysis of these CpGs. Patients of the CIMP-H subgroup had poorer OS and RFS, while patients of CIMP-L subgroup had better OS and RFS. The CIMP status were also an independent prognostic factors for OS and PFS. In molecular features, significantly higher somatic mutation burdens and tumor mutational burden were found at patients of CIMP-H subgroup compared to that in patients of CIMP-L subgroup. Besides, lower stromal score, immune score and higher cancer stemness indices and tumor purity were also found at patients of CIMP-H subgroup compared to that in patients of CIMP-L subgroup. Correspondingly, significantly total T cells, total B cells, CD8 T cells, memory CD4 T cells and higher regulatory T cells were found at patients of CIMP-H subgroup. Moreover, significantly lower expression of immune checkpoint genes, such as PD-1, CTLA4, CD86, VTCN1 and LAG-3 were also found at patients of CIMP-H subgroup compared to that in patients of CIMP-L subgroup. In the end, we validated the CIMP status in PC patients of ICGC dataset.ConclusionThree distinct CIMP subgroups of PC patients with distinct clinical characteristic, prognosis, gene mutation landscape and TME were identified and validated. The CIMP may help to make an assertion to provide specific and efficient treatment options for patients of different subtypes.

show abstract

Synergistic effects of the combination of 5-Aza‑CdR and suberoylanilide hydroxamic acid on the anticancer property of pancreatic cancer

Cited by 9 publications

References 34 publications

A novel feedback loop between high MALAT-1 and low miR-200c-3p promotes cell migration and invasion in pancreatic ductal adenocarcinoma and is predictive of poor prognosis

A novel feedback loop between high MALAT-1 and low miR-200c-3p promotes cell migration and invasion in pancreatic ductal adenocarcinoma and is predictive of poor prognosis

Thymoquinone-Induced Reactivation of Tumor Suppressor Genes in Cancer Cells Involves Epigenetic Mechanisms

Cpg Island Methylator Phenotype With Distinctly Different Prognosis And Molecular Features In Pancreatic Cancer Patient

Contact Info

Product

Resources

About