Role of Gene Therapy in Pancreatic Cancer—A Review

Sato-Dahlman, Mizuho; Wirth, Keith; Yamamoto, Masato

doi:10.3390/cancers10040103

Cited by 23 publications

(19 citation statements)

References 109 publications

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“…PCa is one of the highly lethal malignancies with extremely low 5-year survival rate (37)(38)(39)(40).…”

Section: Discussionmentioning

confidence: 99%

microRNA-26a Inhibits the Malignant Tumor Behavior of Pancreatic Cancer Cells via Targeting E2F7

Wang

Chen

2020

Preprint

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Abstract Background: Dysregulation of microRNAs (miRNAs) plays important roles in the development of pancreatic cancer (PCa). miR-26a was reported as a tumor suppressor in multiple cancers. The aim of this study was to explore the potential role and molecular mechanism of miR-26a in the progression of PCa.Methods: The expression of miR-26a in PCa tissues and cells was detected by RT-qPCR. The effects of miR-26a on the growth of PCa cells were determined by the cell counting kit-8 (CCK-8) assay, colony formation and flow cytometry. The targets of miR-26a were predicted by miRDB database and confirmed by luciferase report assay. The protein level was detected by western blot. CHIP assay was performed to detect the effects of miR-26 on the transcription of E2F7 targets.Results: miR-26a was down-regulated in PCa tissues and cell lines. Ectopic expressed miR-26a suppressed the proliferation, colony formation and the tumor stem cell properties of PCa cells. The transcription factor E2F7 was identified as a target of miR-26a. MiR-26a bound the 3’-untranslated region (UTR) of E2F7 and inhibited the expression of E2F7 in PCa cells. Decreased miR-26a in PCa tissues was inversely correlated with that of E2F7. miR-26a transcriptionally reduced the expression of VEGFA via suppressing the binding of E2F7 with the promoter of VEGFA. Overexpression of E2F7 attenuated the suppressive role of miR-26a in the proliferation of PCa cells. Consistently, knockout of E2F7 further significantly inhibited the growth of PCa cells combined with miR-26a overexpression.Conclusion: Our results uncovered the novel function of miR-26a/E2F7/VEGFA in the malignancy of PCa, suggesting miR-26a as a potential target for the treatment of patients with PCa.

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“…PCa is one of the highly lethal malignancies with extremely low 5-year survival rate (37)(38)(39)(40).…”

Section: Discussionmentioning

confidence: 99%

microRNA-26a Inhibits the Malignant Tumor Behavior of Pancreatic Cancer Cells via Targeting E2F7

Wang

Chen

2020

Preprint

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“…Silencing upregulated miRNA-21 and miRNA-221 in PDAC cells lines with antisense oligonucleotides also led to a significant inhibition of primary tumor growth and metastasis in gemcitabine resistant cells (24). Although miRNA-based therapy has been tested in preclinical studies, at present no clinical trials have been performed to test its use against PDAC (25).…”

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

confidence: 99%

Pancreatic Cancer Heterogeneity Can Be Explained Beyond the Genome

2019

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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.

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“…Currently, research on exosomal drug delivery for PC treatment has mainly focused on loading genetic substances—for example, small interfering RNA (siRNA) and miRNA—into exosomes to inhibit PC progression and metastasis. Recent advances in gene therapies offer novel opportunities for treatment in addition to aggressive chemotherapy and surgical resection, even in patients with locally advanced disease 120. KRAS mutations are demonstrated to occur early in the development of PC, consistently manifesting as a gain-of-function substitution mutation in codon 12 that mutates the glycine residue to aspartate (G12D) 121…”

Section: Exosomes and Pcmentioning

confidence: 99%

Exosomes and pancreatic diseases: status, challenges, and hopes

Guo

Fan

et al. 2019

Int. J. Biol. Sci.

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Pancreatic disease, including pathologies such as acute pancreatitis (AP), chronic pancreatitis (CP), and pancreatic cancer (PC), is a complicated and dangerous clinical condition involving the disruption of exocrine or endocrine function. PC has one of the highest mortality rates among cancers due to insufficient diagnosis in early stages. Furthermore, efficient treatment options for the disease etiologies of AP and CP are lacking. Thus, the identification of new therapeutic targets and reliable biomarkers is required. As essential couriers in intercellular communication, exosomes have recently been confirmed to play an important role in pancreatic disease, but the specific underlying mechanisms are unknown. Herein, we summarize the current knowledge of exosomes in pancreatic disease with respect to diagnosis, molecular mechanisms, and treatment, proposing new ideas for the study of pancreatic disease.

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Role of Gene Therapy in Pancreatic Cancer—A Review

Cited by 23 publications

References 109 publications

microRNA-26a Inhibits the Malignant Tumor Behavior of Pancreatic Cancer Cells via Targeting E2F7

microRNA-26a Inhibits the Malignant Tumor Behavior of Pancreatic Cancer Cells via Targeting E2F7

Pancreatic Cancer Heterogeneity Can Be Explained Beyond the Genome

Exosomes and pancreatic diseases: status, challenges, and hopes

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