A novel epigenetic modulating agent sensitizes pancreatic cells to a chemotherapy agent

Thakar, Manjusha; Hu, Yue; Morreale, Michael; Lerner, Lane; Lin, Wan Ying; Sen, Rupashree; Cai, Yi; Karunasena, Enusha; Saggi, Soren; Keer, Harold; Ahuja, Nita

doi:10.1371/journal.pone.0199130

Cited by 11 publications

(10 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, the effect of DNMT1/miR-29b-3p on cell apoptosis and cycle was not investigated in the present study. Based on previous research, DNMT1 siRNA induces a significant cell viability decrease, leads to a G2-phase block and cell apoptosis in pancreatic cancer (10,52), indicating that this axis may promote cell survival. Further study will focus on this aspect.…”

Section: Discussionmentioning

confidence: 84%

Methylation of the miR‑29b‑3p promoter contributes to angiogenesis, invasion, and migration in pancreatic cancer

Wang

2020

Oncol Rep

View full text Add to dashboard Cite

The aim of the present study was to investigate the effects of microRNA (miR)-29b-3p gene promoter methylation on angiogenesis, invasion, and migration in human pancreatic cancer. Prediction of promoter methylation of miR-29b-3p was performed through the MethPrimer tool. Then the methylation levels of miR-29b-3p in human pancreatic cancer tissues and cell lines were detected by pyrosequencing, and the relative expression of miR-29b-3p was assessed in pancreatic cancer tissues by qPCR. The results were analyzed by linear regression. Western blot analysis was used to detect expression of DNA methyltransferases (DNMTs) in pancreatic cancer tissues and adjacent tissues. The Transwell assay was used to detect the ability of cell migration and invasion. Cells were co-cultured with human umbilical vein endothelial cells (HUVECs) to detect the ability of angiogenesis. The results revealed that DNMT1 expression in pancreatic cancer tissues was higher than that in adjacent tissues. Further results showed that expression of miR-29b was negatively correlated with the methylation level of the miR-29b promoter. Bxpc3 and Capan-2 cells had higher methylation levels, and the expression level of miR-29b-3p in Bxpc3 and Capan-2 cells was found to be lower than that of other cell lines. Expression of zonula occludens-1 (ZO-1) and occludin was significantly increased, and the migration of cancer cells was decreased after cells were treated with siRNA DNMT1. Further results showed that miR-29b reversed the promotive effect of DNMT1 overexpression on tumor cell malignant properties. Methylation of the miR-29b-3p promoter contributes to angiogenesis, invasion, and migration in pancreatic cancer. This study indicated that the alteration of methylation of mR-19b may be a potential approach for inhibiting the progression of pancreatic cancer.

show abstract

Section: Discussionmentioning

confidence: 84%

Methylation of the miR‑29b‑3p promoter contributes to angiogenesis, invasion, and migration in pancreatic cancer

Wang

2020

Oncol Rep

View full text Add to dashboard Cite

show abstract

“…In pancreatic cancer cell lines with low DNMT1 expression, the DNMT inhibitor decitabine depletes DNMT1 and exerts anti-tumor effects [ 25 ]. While guadecitabine sensitizes pancreatic cancer cells to chemotherapeutic agents [ 29 ], there is only one phase I study evaluating the anti-tumor effect of DNMT inhibitor on pancreatic cancer [ 30 ].…”

Section: Dna Methylationmentioning

confidence: 99%

Epigenetic regulation of pancreatic adenocarcinoma in the era of cancer immunotherapy

2022

View full text Add to dashboard Cite

Pancreatic adenocarcinoma is a lethal cancer with poor response to chemotherapy and immune checkpoint inhibitors. Recent studies suggest that epigenetic alterations contribute to its aggressive biology and the tumor microenvironment which render it unresponsive to immune checkpoint blockade. Here, we review our current understandings of epigenetic dysregulation in pancreatic adenocarcinoma, its effect on the tumor immune microenvironment, and the potential for epigenetic therapy to be combined with immune checkpoint inhibitors.

show abstract

“…However, zebularine drives PDAC stem cells to a more proliferative phenotype with increased sensitivity to current chemotherapies. A recent study (35) also showed an improvement in the response of MIA PaCa-2 and PANC-1 cell lines to irinotecan after sensitization with guadecitabine (SGI-110), a next generation epigenetic modulator with a longer half-life and better tolerability than 5-AZA (36). Nevertheless, data obtained from modifying DNA methylation patterns in cell lines may not reflect the heterogeneity present among patients and so, its extrapolation to clinics is uncertain.…”

Section: The Epigenetic Landscape Underlying Pdac As a Target For Patmentioning

confidence: 99%

Pancreatic Cancer Heterogeneity Can Be Explained Beyond the Genome

2019

View full text Add to dashboard Cite

Pancreatic ductal adenocarcinoma (PDAC) remains a major health problem because it induces almost systematic mortality. Carcinogenesis begins with genetic aberrations which trigger epigenetic modifications. While genetic mutations initiate tumorigenesis, they are unable to explain the vast heterogeneity observed among PDAC patients. Instead, epigenetic changes drive transcriptomic alterations that can regulate the malignant phenotype. The contribution of factors from the environment and tumor microenvironment defines different epigenetic landscapes that outline two clinical subtypes: basal, with the worst prognosis, and classical. The epigenetic nature of PDAC, as a reversible phenomenon, encouraged several studies to test epidrugs. However, these drugs lack specificity and although there are epigenetic patterns shared by all PDAC tumors, there are others that are specific to each subtype. Molecular characterization of the epigenetic mechanisms underlying PDAC heterogeneity could be an invaluable tool to predict personalized therapies, stratify patients and search for novel therapies with more specific phenotype-based targets. Novel therapeutic strategies using current anticancer compounds or existing drugs used in other pathologies, alone or in combination, could be used to kill tumor cells or convert aggressive tumors into a more benign phenotype.

show abstract

A novel epigenetic modulating agent sensitizes pancreatic cells to a chemotherapy agent

Cited by 11 publications

References 47 publications

Methylation of the miR‑29b‑3p promoter contributes to angiogenesis, invasion, and migration in pancreatic cancer

Methylation of the miR‑29b‑3p promoter contributes to angiogenesis, invasion, and migration in pancreatic cancer

Epigenetic regulation of pancreatic adenocarcinoma in the era of cancer immunotherapy

Pancreatic Cancer Heterogeneity Can Be Explained Beyond the Genome

Contact Info

Product

Resources

About