miR-223 and Chromogranin A Affect Inflammatory Immune Cell Activation in Liver Metastasis of Neuroendocrine Neoplasms Article Swipe
Lukas Geisler
,
Katharina Detjen
,
Teresa Hellberg
,
Marlene Kohlhepp
,
Carsten Grötzinger
,
Jana Knorr
,
I Eichhorn
,
Raphael Mohr
,
Theresa Maria Holtmann
,
Bertram Wiedenmann
,
Frank Tacke
,
Christoph Roderburg
,
Alexander Wree
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.3390/cells14020111
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.3390/cells14020111
Neuroendocrine neoplasms (NENs) are a diverse group originating from endocrine cells/their precursors in pancreas, small intestine, or lung. The key serum marker is chromogranin A (CgA). While commonly elevated in patients with NEN, its prognostic value is still under discussion. Secretion/posttranslational proteolytic cleavage of CgA results in multiple bioactive fragments, which are essential regulators of the cardiovascular and immune system. miR-223, regulator of Nrlp3 inflammasome and neutrophil activation, was recently found to have decreased in patients with NEN. We performed flow cytometry of circulating neutrophils in a patient cohort (n = 10) with NEN, microdissection and histology of tumor tissue. Subsequently, in vitro transfections using the well-established human pancreatic NEN cell line (BON), and co-culture experiments with primary macrophages and neutrophils were performed. Serum miR-223 in patients correlated with the expression of the neutrophil activation marker CD15 in circulating cells. Neutrophilic CD62L/CD63 showed good discrimination compared to healthy controls. Immune cell-derived miR-155, miR-193 and miR-223 colocalize with neutrophil in the extra-tumoral tissue alongside Nlrp3-associated caspase-1 activation. miR-223 knockdown in BON decreased the CgA intracellularly, increased in cellular granularity and caspase-1 activation. Plasmin inhibitor a2-aP reverted those effects. Western Blot showed fragmented CgA following miR-223 knockdown, which altered the inflammatory potential of neutrophils. Our data hence provide initial insights into an immunoregulatory mechanism via miR-223 and CgA in NEN cells, as regulation of miR-223 in NEN may affect tumor-associated inflammation.
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Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.3390/cells14020111
- https://www.mdpi.com/2073-4409/14/2/111/pdf?version=1736827798
- OA Status
- gold
- References
- 81
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4406375887
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W4406375887Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.3390/cells14020111Digital Object Identifier
- Title
-
miR-223 and Chromogranin A Affect Inflammatory Immune Cell Activation in Liver Metastasis of Neuroendocrine NeoplasmsWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2025Year of publication
- Publication date
-
2025-01-14Full publication date if available
- Authors
-
Lukas Geisler, Katharina Detjen, Teresa Hellberg, Marlene Kohlhepp, Carsten Grötzinger, Jana Knorr, I Eichhorn, Raphael Mohr, Theresa Maria Holtmann, Bertram Wiedenmann, Frank Tacke, Christoph Roderburg, Alexander WreeList of authors in order
- Landing page
-
https://doi.org/10.3390/cells14020111Publisher landing page
- PDF URL
-
https://www.mdpi.com/2073-4409/14/2/111/pdf?version=1736827798Direct link to full text PDF
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-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://www.mdpi.com/2073-4409/14/2/111/pdf?version=1736827798Direct OA link when available
- Concepts
-
Chromogranin A, Immune system, Biology, Inflammation, Cancer research, Gene knockdown, Flow cytometry, Apoptosis, Immunology, Immunohistochemistry, BiochemistryTop concepts (fields/topics) attached by OpenAlex
- Cited by
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0Total citation count in OpenAlex
- References (count)
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81Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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| publication_year | 2025 |
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