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Menin 在癌症中的作用。

Menin in Cancer.

机构信息

Division of Gastroenterology and Hepatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Department of Cancer Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

出版信息

Genes (Basel). 2024 Sep 21;15(9):1231. doi: 10.3390/genes15091231.


DOI:10.3390/genes15091231
PMID:39336822
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11431421/
Abstract

The protein menin is encoded by the 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 , 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.

摘要

Menin 蛋白由 基因编码,主要作为核支架蛋白,通过与染色质修饰物和转录因子相互作用及其调节来调节基因表达。尽管 menin 的功能范围不断扩大,但 menin 在癌症中的作用是一个日益受到关注的领域。menin 越来越被认为具有双重功能,即在高度依赖肿瘤和特定背景的情况下,作为肿瘤抑制因子或肿瘤促进因子发挥作用。虽然 menin 作为神经内分泌肿瘤生长的抑制因子,如多发性内分泌肿瘤 1 型(MEN1)综合征(由 的致病性种系变异引起)中所见,但最近的数据表明,menin 还抑制胆管癌、胰腺导管腺癌、胃腺癌、肺腺癌和黑色素瘤。另一方面,menin 也可以作为白血病、结直肠癌、卵巢和子宫内膜癌、尤文肉瘤和神经胶质瘤中的肿瘤促进因子。此外,menin 可根据激素受体状态在乳腺和前列腺中抑制或促进肿瘤发生,在肝细胞癌中也可能具有混合作用。在这里,我们综述了关于 menin 在广泛不同癌症类型中的作用和功能的快速发展的文献,概述了 menin 功能和作用机制的肿瘤特异性差异,并确定了其治疗潜力,并强调了未来研究的领域。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b96/11431421/669159535f3c/genes-15-01231-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b96/11431421/669159535f3c/genes-15-01231-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b96/11431421/669159535f3c/genes-15-01231-g001.jpg

相似文献

[1]
Menin in Cancer.

Genes (Basel). 2024-9-21

[2]
A Review of the Scaffold Protein Menin and its Role in Hepatobiliary Pathology.

Gene Expr. 2017-7-7

[3]
In search of tumor suppressing functions of menin.

Mol Cell Endocrinol. 2007-2

[4]
Mechanisms of disease: multiple endocrine neoplasia type 1-relation to chromatin modifications and transcription regulation.

Nat Clin Pract Endocrinol Metab. 2006-10

[5]
Menin molecular interactions: insights into normal functions and tumorigenesis.

Horm Metab Res. 2005-6

[6]
Role of miR-24 in Multiple Endocrine Neoplasia Type 1: A Potential Target for Molecular Therapy.

Int J Mol Sci. 2021-7-8

[7]
Menin epigenetically represses Hedgehog signaling in MEN1 tumor syndrome.

Cancer Res. 2013-4-11

[8]
Multiple endocrine neoplasia type 1.

Front Horm Res. 2013-3-19

[9]
Multiple endocrine neoplasia type 1 associated with a new germline Men1 mutation in a family with atypical tumor phenotype.

Hormones (Athens). 2016

[10]
Tissue selectivity in multiple endocrine neoplasia type 1-associated tumorigenesis.

Cancer Res. 2009-8-15

引用本文的文献

[1]
Decoding Pancreatic Neuroendocrine Tumors: Molecular Profiles, Biomarkers, and Pathways to Personalized Therapy.

Int J Mol Sci. 2025-8-13

[2]
Prognostic Impact of Phenotypic and Genetic Features of Pancreatic Malignancies.

Life (Basel). 2025-4-11

[3]
An Analysis of Primary Hyperparathyroidism in Individuals Diagnosed with Multiple Endocrine Neoplasia Type 2.

Diseases. 2025-3-27

[4]
Targeting the Menin-KMT2A interaction in leukemia: Lessons learned and future directions.

Int J Cancer. 2025-1-30

[5]
Menin Inhibitors: New Targeted Therapies for Specific Genetic Subtypes of Difficult-to-Treat Acute Leukemias.

Cancers (Basel). 2025-1-4

本文引用的文献

[1]
Menin Inhibition With Revumenib for -Rearranged Relapsed or Refractory Acute Leukemia (AUGMENT-101).

J Clin Oncol. 2025-1

[2]
Distinct Responses to Menin Inhibition and Synergy with DOT1L Inhibition in -Rearranged Acute Lymphoblastic and Myeloid Leukemia.

Int J Mol Sci. 2024-5-30

[3]
Multiple Endocrine Neoplasia Type 1 Regulates TGFβ-Mediated Suppression of Tumor Formation and Metastasis in Melanoma.

Cells. 2024-6-4

[4]
MEN1 deficiency stabilizes PD-L1 and promotes tumor immune evasion of lung cancer.

Cancer Sci. 2024-8

[5]
A 2024 Update on Menin Inhibitors. A New Class of Target Agents against KMT2A-Rearranged and NPM1-Mutated Acute Myeloid Leukemia.

Hematol Rep. 2024-4-18

[6]
Synergistic Effects of the RAR Agonist Tamibarotene and the Menin Inhibitor Revumenib in Acute Myeloid Leukemia Cells with KMT2A Rearrangement or NPM1 Mutation.

Cancers (Basel). 2024-3-28

[7]
Combined deletion of MEN1, ATRX and PTEN triggers development of high-grade pancreatic neuroendocrine tumors in mice.

Sci Rep. 2024-4-12

[8]
CRL4DCAF4 E3 ligase-mediated degradation of MEN1 transcriptionally reactivates hTERT to sustain immortalization in colorectal cancer cells.

Carcinogenesis. 2024-8-12

[9]
MLL1 regulates cytokine-driven cell migration and metastasis.

Sci Adv. 2024-3-15

[10]
BRG1/BRM inhibitor targets AML stem cells and exerts superior preclinical efficacy combined with BET or menin inhibitor.

Blood. 2024-5-16

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