Background/aim: The entire mechanisms by which epigenetic modifiers contribute to the development of pancreatic cancer remain unknown. Although the histone methyltransferase G9a is a promising target in human cancers, its role in pancreatic carcinogenesis has been under-studied. The aim of the study was to examine the role of G9a in pancreatic carcinogenesis by a gene-targeting mouse model.
Materials And Methods: We established pancreas-specific G9a mice and crossed them with Ptf1a; Kras (KC) mice, which spontaneously develop pancreatic cancer. The phenotypes of the resulting KC mice with G9a deletion were examined. We analyzed transcriptomic data by microarray and genome-wide chromatin accessibility by transposase-accessible chromatin using sequencing. We established pancreatic organoids from KC mice.
Results: G9a deficiency impaired the progression of pancreatic intraepithelial neoplasia (PanIN) and prolonged the survival of KC mice. The number of phosphorylated Erk-positive cells and Dclk1-positive cells, which are reported to be essential for the progression of PanIN, were decreased by G9a deletion. UNC0638, an inhibitor of G9a, suppressed the growth of organoids and increased global chromatin accessibility, especially around the regions including the protein phosphatase 2A genes.
Conclusion: Thus, our study suggested the functional interaction of G9a, Dclk1 and Mapk pathway in the Kras-driven pancreatic carcinogenesis. The inhibition of G9a may suppress the initiation of oncogenic Kras-driven pancreatic carcinogenesis.
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http://dx.doi.org/10.21873/cgp.20224 | DOI Listing |
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December 2024
State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-Products, School of Marine Sciences, Ningbo University, Ningbo 315211, China.
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February 2025
Department of Medical Laboratory, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong 524000, P.R. China.
Pancreatic cancer is an aggressive tumor, which is often associated with a poor clinical prognosis and resistance to conventional chemotherapy. Therefore, there is a need to identify new therapeutic markers for pancreatic cancer. Although KIN17 is a highly expressed DNA‑ and RNA‑binding protein in a number of types of human cancer, its role in pancreatic cancer development, especially in relation to progression, is currently unknown.
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January 2025
The First Department of Thoracic Surgery, Hunan Cancer Hospital and the affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, PR China.
Angiogenesis is a significant character of lung adenocarcinoma (LUAD) and is an important reason leading to high mortality rates of LUAD patients. However, the molecular mechanisms of lncRNAs regulating the angiogenesis in LUAD have not been fully elucidated. Here we show lncRNA chromatin-associated RNA 10 (CAR10) was upregulated in the tumor tissue of patients with LUAD and enhanced tumor metastasis.
View Article and Find Full Text PDFBackground: Autoimmune pancreatitis (AIP) is a form of chronic pancreatitis that presents clinically with obstructive icterus, histologically with infiltration of pancreatic parenchyma by inflammatory cells leading to chronic inflammation with fibrosis, and therapeutically with good response to corticosteroid therapy. Clinically, it may resemble malignant disease, making diagnosis difficult and requiring a multidisciplinary team (gastroenterologist, endoscopist, radiologist, surgeon, pathologist). Two types of AIP are distinguished.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
National "111" Center for Cellular Regulation and Molecular Pharmaceutics, Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei University of Technology, Wuhan 430068, China.
Pancreatic cancer remains one of the most lethal forms of cancer. Currently, there is a lack of effective drug treatments for pancreatic cancer. However, as a newly discovered form of non-apoptotic cell death, ferroptosis has garnered increasing attention in relation to pancreatic cancer.
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