The link between menin and pleiotrophin in the tumor biology of pancreatic neuroendocrine neoplasms

He, Liu; Boulant, Steeve; Stanifer, Megan L.; Guo, Cheng; Nießen, Anna; Chen, Mingyi; Felix, Klaus; Bergmann, Frank; Strobel, Oliver; Schimmack, Simon

doi:10.1111/cas.15301

Cited by 3 publications

(1 citation statement)

References 65 publications

(116 reference statements)

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“…MEN1 is considered a tumor suppressor gene [ 29 ]. MEN1 is the most frequently mutated gene in pancreatic neuroendocrine neoplasms (pNEN) [ 30 ] and its function has also been suggested in diverse familial and sporadic tumors of endocrine origin [ 31 ]. Menin protein binds and regulates several genes, including telomerase reverse transcriptase (hTERT), Hox family genes, and the cyclin-dependent kinase inhibitor genes p27 and p18.…”

Section: Discussionmentioning

confidence: 99%

Deep Learning Techniques to Characterize the RPS28P7 Pseudogene and the Metazoa-SRP Gene as Drug Potential Targets in Pancreatic Cancer Patients

Salgado,

Prado Montes de Oca,

Chairez

et al. 2024

Biomedicines

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The molecular explanation about why some pancreatic cancer (PaCa) patients die early and others die later is poorly understood. This study aimed to discover potential novel markers and drug targets that could be useful to stratify and extend expected survival in prospective early-death patients. We deployed a deep learning algorithm and analyzed the gene copy number, gene expression, and protein expression data of death versus alive PaCa patients from the GDC cohort. The genes with higher relative amplification (copy number >4 times in the dead compared with the alive group) were EWSR1, FLT3, GPC3, HIF1A, HLF, and MEN1. The most highly up-regulated genes (>8.5-fold change) in the death group were RPL30, RPL37, RPS28P7, RPS11, Metazoa_SRP, CAPNS1, FN1, H3−3B, LCN2, and OAZ1. None of their corresponding proteins were up or down-regulated in the death group. The mRNA of the RPS28P7 pseudogene could act as ceRNA sponging the miRNA that was originally directed to the parental gene RPS28. We propose RPS28P7 mRNA as the most druggable target that can be modulated with small molecules or the RNA technology approach. These markers could be added as criteria to patient stratification in future PaCa drug trials, but further validation in the target populations is encouraged.

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Section: Discussionmentioning

confidence: 99%

Deep Learning Techniques to Characterize the RPS28P7 Pseudogene and the Metazoa-SRP Gene as Drug Potential Targets in Pancreatic Cancer Patients

Salgado,

Prado Montes de Oca,

Chairez

et al. 2024

Biomedicines

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The link between menin and pleiotrophin in the tumor biology of pancreatic neuroendocrine neoplasms

Boulant

Stanifer

et al. 2022

Cancer Science

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MEN1, which encodes menin protein, is the most frequently mutated gene in pancreatic neuroendocrine neoplasms (pNEN). Pleiotrophin (PTN) has been reported as a downstream factor of menin that promotes metastasis in different tumor entities. In this study, the effect of menin and its link to PTN were assessed using features of pNEN cells and the outcome of patients with pNEN. The expression levels of menin and PTN in tissues from patients with pNEN were examined using qRT‐PCR and western blot and compared with their metastasis status. Functional assays, including transwell migration/invasion and scratch wound‐healing assays, were performed on specifically designed CRISPR/Cas9‐mediated MEN1‐knockout (MEN1‐KO) pNEN cell lines (BON1MEN1‐KO and QGP1MEN1‐KO) to study the metastasis of pNEN. Among 30 patients with menin‐negative pNEN, 21 revealed a strong protein expression of PTN. This combination was associated with metastasis and shorter disease‐free survival. Accordingly, in BON1MEN1‐KO and QGP1MEN1‐KO cells, PTN protein expression was positively associated with enhanced cell migration and invasion, which could be reversed using PTN silencing. PTN is a predicting factor of metastatic behavior of menin‐deficient‐pNEN. In vitro, menin is able to both promote and suppress the metastasis of pNEN by regulating PTN expression depending on the tumoral origin of pNEN cells.

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Menin in Cancer

Majer,

Hua,

Katona

2024

Genes

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The protein menin is encoded by the MEN1 gene and primarily serves as a nuclear scaffold protein, regulating gene expression through its interaction with and regulation of chromatin modifiers and transcription factors. While the scope of menin’s functions continues to expand, one area of growing investigation is the role of menin in cancer. Menin is increasingly recognized for its dual function as either a tumor suppressor or a tumor promoter in a highly tumor-dependent and context-specific manner. While menin serves as a suppressor of neuroendocrine tumor growth, as seen in the cancer risk syndrome multiple endocrine neoplasia type 1 (MEN1) syndrome caused by pathogenic germline variants in MEN1, recent data demonstrate that menin also suppresses cholangiocarcinoma, pancreatic ductal adenocarcinoma, gastric adenocarcinoma, lung adenocarcinoma, and melanoma. On the other hand, menin can also serve as a tumor promoter in leukemia, colorectal cancer, ovarian and endometrial cancers, Ewing sarcoma, and gliomas. Moreover, menin can either suppress or promote tumorigenesis in the breast and prostate depending on hormone receptor status and may also have mixed roles in hepatocellular carcinoma. Here, we review the rapidly expanding literature on the role and function of menin across a broad array of different cancer types, outlining tumor-specific differences in menin’s function and mechanism of action, as well as identifying its therapeutic potential and highlighting areas for future investigation.

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The link between menin and pleiotrophin in the tumor biology of pancreatic neuroendocrine neoplasms

Cited by 3 publications

References 65 publications

Deep Learning Techniques to Characterize the RPS28P7 Pseudogene and the Metazoa-SRP Gene as Drug Potential Targets in Pancreatic Cancer Patients

Deep Learning Techniques to Characterize the RPS28P7 Pseudogene and the Metazoa-SRP Gene as Drug Potential Targets in Pancreatic Cancer Patients

The link between menin and pleiotrophin in the tumor biology of pancreatic neuroendocrine neoplasms

Menin in Cancer

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