REG3A promotes the development of pancreatic cancer by activating EGFR pathway
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE282763 | GEO | 2025/02/26
REPOSITORIES: GEO
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Project description:REG3A promotes the development of pancreatic cancer by activating EGFR pathway
| PRJNA1190379 | ENA
Project description:Paneth cell metaplasia (PCM) is a phenomenon in which Paneth cells, typically found in the small intestine, appear in the colonic epithelium of patients with ulcerative colitis (UC). Our study demonstrates that the PCM occurrence correlates with disease duration and active inflammation. Furthermore, we reveal that the inflammation-induced cytokine IL-22 suppresses Notch signaling, thereby promoting PCM formation in the colonic epithelium while simultaneously inducing REG3A expression in metaplastic niches. In vitro, we show that Reg3a directly enhances cell proliferation and promotes wound healing using mouse colonic organoids. In vivo, Reg3aΔIEC mice in both acute and chronic DSS-induced colitis models exhibit delayed wound healing. Additionally, studies conducted with patient-derived human colonic organoids revealed that REG3A administration stimulates cell proliferation and accelerates wound healing. These findings underscore a novel protective role of PCM-mediated REG3A in the colonic epithelium of patients with UC.
2025-12-02 | GSE311760 | GEO
Project description:Paneth cell metaplasia (PCM) is a phenomenon in which Paneth cells, typically found in the small intestine, appear in the colonic epithelium of patients with ulcerative colitis (UC). Our study demonstrates that the PCM occurrence correlates with disease duration and active inflammation. Furthermore, we reveal that the inflammation-induced cytokine IL-22 suppresses Notch signaling, thereby promoting PCM formation in the colonic epithelium while simultaneously inducing REG3A expression in metaplastic niches. In vitro, we show that Reg3a directly enhances cell proliferation and promotes wound healing using mouse colonic organoids. In vivo, Reg3aΔIEC mice in both acute and chronic DSS-induced colitis models exhibit delayed wound healing. Additionally, studies conducted with patient-derived human colonic organoids revealed that REG3A administration stimulates cell proliferation and accelerates wound healing. These findings underscore a novel protective role of PCM-mediated REG3A in the colonic epithelium of patients with UC.
2025-12-03 | GSE312352 | GEO
Project description:The human C-type lectin Reg3a (HIP/PAP) is an antimicrobial peptide that kills Gram-positive bacteria. Reg3a preserves gut microbiota homeostasis, reinforces intestinal barrier function and thereby helps to fight induced colitis in mice. Transcriptomic data revealed an upregulation of numerous genes involved in the robustness of the intestinal barrier, and the biosynthesis pathway of mucin core 1 and 3 O-glycans.
2018-01-31 | GSE64932 | GEO
Project description:Antimicrobial proteins of the REG3 family represent, like a wide variety of C-type lectins to which they belong, the first line of protection against infections and transformed cells. Their expression is inducible, particularly in response to inflammation, making their role in cancer biology less clear and controversial, as an immune-inflammation background may pre-exist or co-exist. We show that REG3A presents a suppressive role of REG3A in hepatocellular carcinoma (HCC) in a mouse models of HCC driven by c-MYC. By comparing the transcriptional profiles of liver tumors from MYC-REG3A-TG mice with those from MYC-TG mice, we found that MYC-REG3A tumors belonged to the S3 and G5 molecular subclasses of the human HCC classification proposed by Hoshida et al. and Boyault et al., respectively, subclasses that concentrate well-differentiated and CTNNB1-mutated HCCs. Tumors from MYC-TG mice exhibited features of S1 and G2/G3 subclasses. Results of the GSEA analysis indicate marked differential gene expression profiles. MYC-REG3A tumors and adjacent liver are enriched in metabolic pathways including bile acid, xenobiotic, and fatty acid metabolism, oxidative phosphorylation, and activation of Wnt/β-catenin signaling, whereas transcriptional reprogramming of MYC-TG mouse livers resulted in activation of cell cycle-, inflammation-, and glycolysis-related pathways as expected.
2024-12-31 | GSE232521 | GEO
Project description:Expression data from pairwise non-tumor and tumor liver of -MYC and C-MYC/REG3A transgenic mice
| PRJNA972660 | ENA
Project description:Prostate cancer is one of the most common tumors of the male genitourinary system. Emerging research have confirmed that circRNAs play an important role in the occurrence and development of tumors. However, the correlation of circular RNA with PCa remains unclear. Here, the circRNA expression profiles in PCa and paracancerous tissues were established by high-throughput sequencing.
2022-01-12 | GSE179321 | GEO
Project description:BackgroundRegenerating family member 3A (REG3A) is involved in the development of multiple malignant tumors, including pancreatic ductal adenocarcinoma (PDAC). However, any role of REG3A in PDAC remains controversial due to its unclear tissue localization or direct receptors, and complex downstream signal transductions.MethodsMorphological analysis and public multi-omics data retrieval were was utilized to elucidate the tissue localization of REG3A in PDAC. To ascertain the pro-oncogenic role of secreted REG3A, experiments were conducted using in vitro PDAC cell lines and in vivo tumor formation assays in nude mice. A battery of investigative techniques, including RNA sequencing, phospho-kinase arrays, western blot analyses, in silico docking simulations, gene truncation strategies, and co-immunoprecipitation, were employed to delve into the downstream signaling transduction pathways induced by REG3A.ResultsIn this study, we confirmed an association between increased serum levels of REG3A and poor prognosis in patients with PDAC. Morphological staining and bioinformatic analysis showed that REG3A was mainly expressed in peritumoral acinar cells that were spatially close to tumor region, while it was almost negative in PDAC tumor cells. Peritumoral REG3A expression levels, but not tumoral REG3A, were highly correlated with PDAC progression. Further in vitro experiments including RNA sequencing and molecular biological assays revealed that secreted REG3A could directly bind to the epidermal growth factor receptor (EGFR), an important pro-oncogene involved in cellular proliferation, and subsequently activate the downstream mitogen-activated protein kinase (MAPK) signals to promote PDAC tumor cell growth.ConclusionTaken together, our data indicated that increased expression of REG3A in peritumoral acinar cells acts as a specific event to indicate PDAC progression, and verified EGFR as a possible target of REG3A, providing mechanistic insights into the role of REG3A, the diagnostic method and therapeutic strategy of PDAC.
| S-EPMC11837727 | biostudies-literature
Project description:Pancreatitis is triggered by environmental or cellular stress and is the leading contributor to pancreatic ductal adenocarcinoma. Altered gene expression in response to acinar cell stress determines the severity and duration of pancreatitis. However, it is unclear what factors contribute to this phenomenon. Here, we define a novel role for Activating Transcription Factor 3 (ATF3) during pancreatic injury. ATF3, a key mediator in the unfolded protein response, is robustly expressed in acinar cells during pancreatitis. Targeted deletion of Atf3 altered the molecular response to injury, with Atf3-/- acinar cells maintaining cell organization in response to cerulein, a well-established inducer of pancreatitis. Characterization of the mechanism using chromatin immunoprecipitation followed by Next Generation sequencing (ChIP-seq) identified 11,771 enrichment spots for ATF3, with known transcriptional start sites for >3,000 genes within 5 kb of ATF3 enrichment. Gene ontology analysis revealed a significant representation of ATF3 enrichment to genes affecting cell organization, including Mist1, a molecule required for establishing acinar cell organization. We confirmed a direct interaction of ATF3 to the Mist1 promoter during pancreatitis, and showed that ATF3 is required for altered Mist1 expression in response to injury. Finally, we demonstrate that ATF3 repression of Mist1 involves HDAC5. These findings suggest that ATF3 is a key transcriptional regulator during pancreatitis and promotes loss of the mature acinar cell phenotype in response to pancreatic injury. Two samples were produced from male mice 4 hours after CIP initiation from intraparitoneal injections of cerulein, a ChIP sample using an ATF3 antibody and an IP control.
2015-08-01 | E-GEOD-60250 | biostudies-arrayexpress
Project description:This study aims to find the specific lncRNA molecule relating BMs from LADC in situ tumor to BM tumor tissue using gene chip technology and, combined with biological information database, through the competitive endogenous RNA (ceRNA) mechanism for microRNA (miRNA) related to specific lncRNA, to verify the possible target genes and therefore to explore the role and mechanism of specific lncRNA in BMs from LADC. By detecting the gene expression profiles of lncRNA and mRNA in cancer tissues of five cases of LADC and the paired paracancerous tissue samples, it was found that there were a large number of differentially expressed lncRNAs and mRNAs in LADC tissues and paracancerous tissues. By detecting the gene expression profiles of lncRNA and mRNA in three cases of BMs from LADC and matched paracancerous tissues, it was found that there were significant differences in the expression of lncRNAs and mRNAs between BM tumors of LADC and paracancerous tissues. These findings will provide a scientific basis for the early diagnosis and targeted therapy of BMs from LADC for application in further studies. Differential expression of lncRNAs and mRNAs in cancer tissues of three cases of BMs from LADC and the paired paracancerous tissue samples, it was found that there were a large number of differentially expressed lncRNAs and mRNAs in BMs tissues and paracancerous tissues.
2020-03-06 | GSE146460 | GEO