Molecular Mechanisms of Cell Death in Gastrointestinal Disease

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cellular Pathology".

Deadline for manuscript submissions: closed (30 April 2023) | Viewed by 2934

Special Issue Editor

National Institute of Gastroenterology “S. De Bellis” Research Hospital, Castellana Grotte, Italy
Interests: microRNA; inflammatory bowel disease; gastrointestinal cancer; intestinal permeability
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Special Issue Information

Dear Colleagues,

Cell death is a significant homeostatic factor, mediating the removal of damaged cells, organelles, and proteins. Many studies have focused on the process of cell death, mainly on the activators of apoptosis, and their strictly associated and interacting proteins. However, cells have several options other than apoptosis. Cell death mechanisms include intrinsic apoptosis, extrinsic apoptosis, cellular senescence, mitochondrial permeability transition (MPT)-driven necrosis, NETotic cell death, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, lysosome-dependent cell death, autophagy, immunogenic cell death, and mitotic catastrophe. In gastrointestinal tract, cell death plays a key role in development, tissue homeostasis, inflammation, immunity, and multiple pathophysiological conditions. The molecular mechanisms of cell death in gastrointestinal disease have not been fully elucidated.

This Special Issue will aim to cover novel research exploring all molecular mechanisms of cell death in gastrointestinal disease, including cancer, immune disease and infectious disease. Additionally, this Special Issue will include studies that highlight the innovative cell death-based drug targets and the associated predictive biomarkers. Original research articles, reviews are welcome. 

Dr. Grazia Serino
Guest Editor

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Keywords

  • cell death
  • miRNAs
  • gastrointestinal cancer
  • gastric cancer
  • colorectal cancer
  • esophageal cancer
  • liver cancer
  • pancreatic cancer
  • inflammatory bowel disease
  • in vitro and in vivo model
  • molecular network
  • molecular pathway
  • translational medicine

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Published Papers (1 paper)

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Research

15 pages, 2306 KiB  
Article
Targeting BET Proteins Decreases Hyaluronidase-1 in Pancreatic Cancer
by Krishan Kumar, Deepak Kanojia, David J. Bentrem, Rosa F. Hwang, Jonathan P. Butchar, Susheela Tridandapani and Hidayatullah G. Munshi
Cells 2023, 12(11), 1490; https://doi.org/10.3390/cells12111490 - 27 May 2023
Cited by 4 | Viewed by 2367
Abstract
Background: Pancreatic ductal adenocarcinoma (PDAC) is characterized by the presence of dense stroma that is enriched in hyaluronan (HA), with increased HA levels associated with more aggressive disease. Increased levels of the HA-degrading enzymes hyaluronidases (HYALs) are also associated with tumor progression. In [...] Read more.
Background: Pancreatic ductal adenocarcinoma (PDAC) is characterized by the presence of dense stroma that is enriched in hyaluronan (HA), with increased HA levels associated with more aggressive disease. Increased levels of the HA-degrading enzymes hyaluronidases (HYALs) are also associated with tumor progression. In this study, we evaluate the regulation of HYALs in PDAC. Methods: Using siRNA and small molecule inhibitors, we evaluated the regulation of HYALs using quantitative real-time PCR (qRT-PCR), Western blot analysis, and ELISA. The binding of BRD2 protein on the HYAL1 promoter was evaluated by chromatin immunoprecipitation (ChIP) assay. Proliferation was evaluated by WST-1 assay. Mice with xenograft tumors were treated with BET inhibitors. The expression of HYALs in tumors was analyzed by immunohistochemistry and by qRT-PCR. Results: We show that HYAL1, HYAL2, and HYAL3 are expressed in PDAC tumors and in PDAC and pancreatic stellate cell lines. We demonstrate that inhibitors targeting bromodomain and extra-terminal domain (BET) proteins, which are readers of histone acetylation marks, primarily decrease HYAL1 expression. We show that the BET family protein BRD2 regulates HYAL1 expression by binding to its promoter region and that HYAL1 downregulation decreases proliferation and enhances apoptosis of PDAC and stellate cell lines. Notably, BET inhibitors decrease the levels of HYAL1 expression in vivo without affecting the levels of HYAL2 or HYAL3. Conclusions: Our results demonstrate the pro-tumorigenic role of HYAL1 and identify the role of BRD2 in the regulation of HYAL1 in PDAC. Overall, these data enhance our understanding of the role and regulation of HYAL1 and provide the rationale for targeting HYAL1 in PDAC. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Cell Death in Gastrointestinal Disease)
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