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MSI1

Official Full Name
musashi RNA binding protein 1
Organism
Homo sapiens
GeneID
4440
Background
This gene encodes a protein containing two conserved tandem RNA recognition motifs. Similar proteins in other species function as RNA-binding proteins and play central roles in posttranscriptional gene regulation. Expression of this gene has been correlated with the grade of the malignancy and proliferative activity in gliomas and melanomas. A pseudogene for this gene is located on chromosome 11q13. [provided by RefSeq, Jul 2008]

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Detailed Information

In 1990, the first member of the Musashi (Msi) family, Msi1, was identified in the neurological system of Drosophila. In eukaryotes, the human Msi1 N-terminus contains two conserved RNA recognition domains (RNAs), which play an important role in the regulation of post-transcriptional gene expression and can be involved in RNA splicing, polyadenylation, Sequence editing, RNA transport, maintenance of RNA stabilization and degradation, intracellular localization and translational control. 

MSI1, positively regulates the Wnt and Notch signaling pathways by binding to and inhibiting the translation of target mRNA. Figure 1. MSI1, positively regulates the Wnt and Notch signaling pathways by binding to and inhibiting the translation of target mRNA. (Smith, A. R., et al. 2015)

Expression Distribution of Msi1

In mammals, Msi1 protein-positive particles are mainly located in the cytoplasm and nucleus, which can determine cell fate at various points, such as maintaining stem cell characteristics, cell differentiation and tumor formation. Msi1 is highly expressed in many cancers such as hepatocellular carcinoma, colorectal cancer, and atypical teratoid/gravitate tumors. Its role is to promote the growth of tumor cells and inhibit the apoptosis of tumor cells. In normal tissue, its expression is limited to stem cells. Currently, Msi1 is a neural stem cell marker and is also expressed in tissues other than the nervous system. Recent studies have shown that Msi1 is expressed in a variety of pathological tissues other than the nervous system (benign and malignant), and the expression rate of Msi1 in malignant tumors is significantly higher than that in benign lesions. Some scholars have studied the expression of Msi1 in the normal stomach, small intestine and descending intestinal mucosa, and the results suggest that Msi1 may become a tumor cell specific marker. Studies have shown that knocking out Msi1 RNA-binding proteins can arrest tumor growth in vivo, decrease cell proliferation, and increase apoptosis.

Msi1 is a positive regulator of Notch signaling-mediated transcription, and Notch signaling determines cell fate by affecting cell proliferation, differentiation, and apoptosis. However, Notch signaling can activate stimulating cell proliferation and inhibit cell proliferation by regulating cell type-specific and content-related pathways in the cell cycle. Msi1 works together by the following aspects: 1) Enhancing the Notch signaling pathway by inhibiting post-transcriptional translation of m-Numb mRNA, thereby promoting cell self-renewal, proliferation and differentiation potential; 2) Msi1 is specifically associated with the target gene Hes1 of the Notch signaling pathway after transcriptional activation, promoting tumor formation and development; 3) Msi1 binds to the characteristic sequence on the 3'-UTR of p21, inhibits p21 expression and participates in cell cycle regulation; 4) Msi1 also passes A unique autocrine signaling pathway activates Wnt and Notch signaling pathways.

Msi1 and Tumor

In the study of colon cancer, it was found that the expression of Msi1 was induced by the Notch3 mechanism to induce stimulation of DLL4, and the level of Msi1 was increased by inhibiting Numb to maintain Notch1 signal. These observations highlight the regulation of Notch activity as a novel feedforward loop for cancer cells. The study demonstrated the expression of Msi1 protein by immunostaining, immunohistochemistry and RNA, and confirmed that Msi1 is a novel prognostic marker for colon cancer patients, which is abnormally expressed during colon cancer metastasis, indicating that it is a potential therapeutic target. It was found that Msi1 is expressed in human colon cancer SW-480 cells, and silencing Msi1 has a negative regulatory effect on cancer cell proliferation, which can significantly inhibit its growth and proliferation.

References:

  1. Smith, A. R. , Marquez, R. T. , Tsao, W. C. , Pathak, S. , & Xu, L. . (2015). Tumor suppressive microrna-137 negatively regulates musashi-1 and colorectal cancer progression. Oncotarget, 6(14).
  2. Gong, P. , Wang, Y. , Gao, Y. , Gao, M. , Liu, L. , & Qu, P. , et al. (2017). Msi1 promotes tumor progression by epithelial-to-mesenchymal transition in cervical cancer. Human Pathology, S0046817717300151.
  3. Lin, J. C. , Tsai, J. T. , Chao, T. Y. , Ma, H. I. , Chien, C. S. , & Liu, W. H. . (2018). Msi1 associates glioblastoma radioresistance via homologous recombination repair, tumor invasion and cancer stem-like cell properties. Radiotherapy and Oncology.
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