Role of Regenerating Islet-Derived Protein 3A in Gastrointestinal Cancer
Open accessAbstract
Regenerating islet-derived protein 3A (Reg3A), a protein mainly expressed in the digestive system, has been found over-expressed in many kinds of gastrointestinal cancer, including hepatocellular carcinoma, pancreatic cancer, gastric cancer, and colorectal cancer, therefore has been considered as a promising tumor marker. In recent years, considerable attention has been focused on the tumorigenesis effects of Reg3A, which were mainly manifested as cell proliferation promotion, cell apoptosis inhibition, the regulation of cancer cell migration and invasion. In particular, based on the significant up-regulation of Reg3A during pancreatic inflammation as well as its tumorigenic potential, Reg3A has been considered to play a key role in inflammation-linked pancreatic carcinogenesis. In addition, we here systematically generalized the reported Reg3A-related signaling molecules, which included JAK2-STAT3- NF-κB, SOCS3, EXTL3-PI3K-Akt, GSK3β, Wnt/β-catenin as well as some invasion and migration-related genes (Snail, MMP-2, MMP-9, E-cadherin, RhoC, and MTA1). And gp130, EGFR, EXTL3, and Fibronectin 1 might act as potential receptors for Reg3A.
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Reg3a was upregulated in both mutants.
“Reg3a was also upregulated in both mutants, and high levels of Reg3a were previously shown to promote proliferation and tumorigenesis of colorectal and hepatocellular carcinomas42,43.”
From One-step generation of tumor models by base editor multiplexing in adult stem cell-derived organoids (2023) · cites this paper as [43]
The citations attach to the claim about proliferation and tumorigenesis, not to the preceding statement that Reg3a was upregulated in both mutants. In “Proliferation-Promoting Effect of Reg3A” (page unavailable), the review reports increased colorectal cancer-cell proliferation with Reg3A overexpression and reduced tumor growth after Reg3A silencing. Its liver-cancer discussion reports Reg3A expression, but does not establish that high Reg3A promotes hepatocellular carcinoma proliferation or tumorigenesis. (LLM, conf=0.83)
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Zhang, A. M. Y., Chu, K., Daly, B. F., Ruiter, T. J. J., Dou, Y., Yang, J. C. C., de Winter, T. J. J., Chhuor, J., Wang, S., Flibotte, S., et al. (2022) · Figshare · doi:10.6084/m9.figshare.19211345
REG family proteins and immune regulation: current evidence and perspectives
Xu, Z., Chen, Y., & Wang, J. (2026) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2026.154758
Self-citation
- Authors
- Zhang, M.-Y., Wang, J., & Guo, J.
- Affiliations
- Wuhan University of Science and Technology (CN)
- Corresponding author
- Wang, Jun
- ORCID
- Guo, Jie
- Venue
- Frontiers in Oncology
- Publisher
- Frontiers Media SA
- Published
- 2019-12-17
- Volume
- 9
- Pages
- 1449-1449
- ISSN
- 2234-943X (ISSN-L)
- PMC
- PMC6928188
- OpenAlex
- W2996671120
- Cited by
- 45
- References
- 43
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 10 · 2023: 5 · 2022: 8 · 2021: 10 · 2020: 7
- FWCI
- 0.62
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Oncology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Natural Science Foundation of China (71974153, 81602108)
- Topics
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mechanisms of cancer metastasis
- Keywords
- REG3A, gastrointestinal cancer, tumor markers, hepatocellular carcinoma, pancreatic cancer, gastric cancer, colorectal cancer, cell proliferation, apoptosis, cell migration and invasion, SOCS3, GSK3β, Wnt/β-catenin signaling, snails, MMP-2, MMP-9, E-cadherin, RhoC, MTA1, gp130, EGFR, FN1
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