MSI2

Official Full Name

musashi RNA binding protein 2

Organism

Homo sapiens

GeneID

124540

Background

This gene encodes an RNA-binding protein that is a member of the Musashi protein family. The encoded protein is transcriptional regulator that targets genes involved in development and cell cycle regulation. Mutations in this gene are associated with poor prognosis in certain types of cancers. This gene has also been shown to be rearranged in certain cancer cells. [provided by RefSeq, Apr 2016]

Synonyms

MSI2H;

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Detailed Information

The Musashi (MSI) family is an evolutionarily conserved RNA-binding protein that is expressed primarily in a variety of tissue stem/progenitor cells, such as the nervous system, epithelial tissue, and hematopoietic system, regulating stem cell proliferation. As a member of the MSI family, MSI2 is highly homologous to MSI1 in molecular structure. Its agreement on the amino acid sequence of the total amino acid sequence and the RNA binding domain is 75% and 90%.

Physiological Function of MSI2

The Y chromosome sex determination box 2 (Sox2) and octamer binding transcription factor 4 (Oct4) are key factors for self-renewal and differentiation of embryonic stem cells. They synergistically regulate the differentiation and development process of embryonic stem cells. The study found that MSI2 is a Sox2-related protein involved in cellular RNA processing and plays an important role in the self-renewal of embryonic stem cells. The study looked at the cytological changes of embryonic stem cells by knocking out the subtype and subtype b of MSI2. It was found that the MSI2 protein a subtype and subtype b play key roles in the self-renewal process of embryonic stem cells and indicate the expression level of MSI2 protein. Alterations can lead to imbalances in Sox2 and Oct4 and regulate embryonic stem cell proliferation, differentiation and development.

In the central nervous system, MSI2 mainly expresses neural precursor cells in the ventricle and subventricular zone, and also expresses cells in the astrocyte lineage, including ependymal cells, which are involved in the maintenance of neural stem cells. Studies have shown that Sox2 is a key transcription factor for nervous system development, and MSI2 acts as a Sox2-related protein to maintain self-renewal of undifferentiated neural stem cells. In addition, studies have found that MSI2 is still expressed in basal ganglia and in some neuronal cells of neuronal cell lines such as γ-aminobutyric acid (GABA) neuron. However, MSI2 is deleted or down-regulated in most post-mitotic neurons, suggesting that MSI2 may play an important regulatory role in specific neural cell lines.

Figure 1. RNA-binding proteins Msi1 and/or Msi2 are required for colorectal cancer. (Li, N., et al. 2015)

MSI2 and Tumor

MSI2 promotes the growth, proliferation and invasion of brain tumors. Multi-dimensional protein identification technology (MudPIT) was used to identify at least 280 Sox2-related proteins in bronchial cell tumor cell line DAOY, and MSI2 and USP9X were screened out. It was found that knocking out MSI2 and USP9X significantly inhibited medulloblastoma cells. The growth of DAOY and glioma cell lines U87 and U118 is associated with poor prognosis in patients with brain tumors. MSI2 is up-regulated in Hepatitis B virus-associated hepatocellular carcinoma, which is closely related to tumor size, tumor differentiation, recurrence, TNM stage, and vascular invasion.

Guo et al. found that MSI2 is overexpressed in pancreatic cancer cells and promotes its proliferation and migration. KLF4 gene (Krüppel-like factor 4) binds to the promoter region of MSI2 to inhibit its transcription. Therefore, the KLF4-MSI2 signal axis as a research target can provide a new strategy for preventing metastasis and diagnosis of pancreatic cancer. In addition, Yang et al. first demonstrated through experiments that silencing of MSI2 expression significantly reduced tyrosine kinase 2 (Janus Kinase 2, JAK2) and its downstream effector signal transducers and activator 3 (signal transducers) in bladder cancer cell lines. The phosphorylation level of activators of transcription1 and STAT3), while the expression of WASF3 in MSI2 overexpressing tumor cells was significantly higher than that of the control group, which was activated by JAK2/STAT3 signaling pathway to promote cell migration and invasion.

References:

Li, N. , Yousefi, M. , Nakauka-Ddamba, A. , Li, F. , Vandivier, L. , & Parada, K. , et al. (2015). The msi family of rna-binding proteins function redundantly as intestinal oncoproteins. Cell Reports, 13(11), 2440-2455.
Yang, C. , Zhang, W. , Wang, L. , Kazobinka, G. , Han, X. , & Li, B. , et al. (2016). Musashi-2 promotes migration and invasion in bladder cancer via activation of the jak2/stat3 pathway. Laboratory Investigation.
Guo, K. , Cui, J. , Quan, M. , Xie, D. , Jia, Z. , & Wei, D. , et al. (2017). The novel klf4/msi2 signaling pathway regulates growth and metastasis of pancreatic cancer. Clinical Cancer Research an Official Journal of the American Association for Cancer Research, 23(3).

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