Expression of the Neural RNA-Binding Protein Musashi1 in Pediatric Brain Tumors

Nakano, Ayako; Kanemura, Yonehiro; Mori, Kanji; Kodama, Eri; Yamamoto, Akira; Sakamoto, Hiroaki; Nakamura, Yasuhiro; Okano, Hideyuki; Yamasaki, Mami; Arita, Norio

doi:10.1159/000103307

Cited by 37 publications

(27 citation statements)

References 39 publications

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“…Msi-1 is an RNA binding protein which is preferentially expressed in stem-cells, functions as a translational repressor (56)(57)(58), and is widely used as a molecular marker to identify stem cells in embryos and adult tissues (26)(27)(28)(29). In our study, Msi-1 was expressed in five MRT cell lines except TTC642, which originated from a neck mass.…”

Section: Discussionmentioning

confidence: 69%

“…In recent years, the concept of CSC involvement in tumorigenesis has attracted the attention of many researchers. Previous studies have shown that NSC acting as CSC is recognized in CNS (24)(25)(26)(27)(28)(29). In the present study, we examined the expression of NSC markers such as CD133, nestin and Msi-1 before and after 4-HPR induced differentiation in MRT cell lines to elucidate the cytological characteristics of MRT cells that are considered to derive from neuroectodermal origin (8,9,12).…”

Section: Introductionmentioning

confidence: 95%

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Expression of neural stem cell markers in malignant rhabdoid tumor cell lines

Okuno

Ohta²,

Katô³

et al. 2009

Oncol Rep

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Abstract. Malignant rhabdoid tumor (MRT) is considered to display multi-phenotypic characteristics but the true origin of this tumor remains unknown. In recent years, the concept of the cancer stem cell (CSC) has drawn great attention. In the present study we investigated six MRT cell lines (TM87-16, STM91-01, TTC642, TTC549, YAM-RTK-1 and TTC1240), for CD133, nestin and Musashi-1 (Msi-1), which are considered to be CSC as well as neural stem cell (NSC) markers, using assays for cell viability and apoptosis, reverse transcriptional polymerase chain reaction (RT-PCR), semiquantitative PCR and Western blot analysis before and after differentiation-induction with N-(4-hydroxyphenyl) retinamid (4-HPR). Before differentiation-induction with 4-HPR, CD133 was detected in three MRT cell lines, nestin in three cell lines and Msi-1 in five cell lines. In TTC549 after differentiation-induction with 4-HPR, nestin and Msi-1 were down-regulated in a time-dependent manner. Similar downregulation of Msi-1 was recognized in YAM-RTK-1. In STM91-01, CD133 was gradually down-regulated and Msi-1 was down-regulated after a transient increase. Results from our study indicated that 4-HPR might be effective in some MRTs. Expression of NSC markers showed that some MRTs contain a subpopulation of NSC and down-regulation of NSC markers in MRT cells provides supportive evidence that many MRTs could be considered of neuroectodermal origin.

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Section: Discussionmentioning

confidence: 69%

Section: Introductionmentioning

confidence: 95%

Expression of neural stem cell markers in malignant rhabdoid tumor cell lines

Okuno

Ohta²,

Katô³

et al. 2009

Oncol Rep

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“…MSI1 is expressed predominantly in proliferating multipotent neural precursor cells, but not in newly generated postmitotic neurons (35). Nakano et al (36) examined MSI1 expression in human medulloblatomas and ependymomas, suggesting that MSI1 could be a useful marker for characterizing tumor heterogeneity and for examining the analogy between normal NSCs and MSI1 + cells in pediatric brain tumors.…”

Section: Discussionmentioning

confidence: 99%

Analysis of stemness gene expression and CD133 abnormal methylation in neuroblastoma cell lines

et al. 2010

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Abstract. Neuroblastoma is the most common extracranial solid tumor in children, accounting for up to 10% of all childhood malignancies. Cellular heterogeneity is a hallmark of this embryonal cancer, as distinct neural crest lineages can be found within the same tumor sample. The aim of our study was to investigate the presence of a subpopulation of immature cells with features of cancer-like stem cells in 10 neuroblastoma cell lines. RT-PCR and flow cytometry were performed in order to analyze different kinds of 'stemness genes' such as: NESTIN (NES), CD133, SOX-2, BMI1, c-KIT, MELK1, MUSASHI-1 (MSI1), FAS, CD44 and VIMENTIN (VIM). In addition, glial and neuronal markers such as NCAM1, GFAP and B-TUBULIN III (TUBB3) were analyzed. Epigenetic changes within the CD133 (Prominin-1) gene promoter were also analyzed. Neuroblastoma cell lines showed a particular pattern of expression, suggesting the presence of an immature cancer stem cell-like subpopulation. The CD133 protein, commonly used to enrich putative cancer propagating stem cell-like populations in different kinds of solid tumors, presented a half-methylated DNA state in 7 of the 12 neuroblastoma cell lines analyzed. An increase in RNA and protein levels of CD133 was achieved following demethylation by assays using 5-aza-2'-deoxycytidine (5-Aza-dC). Since cancer stem cells are believed to be responsible for tumor metastasis, escape from anticancer therapies and disease relapse, their therapeutic targeting and analysis is crucial in neuroblastoma. Moreover, the regulation of CD133 by epigenetic changes may provide an innovative mechanism of CD133 expression as its regulation still remains unclear.

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“…A disease of great relevance to Msi1 is cancer, because many carcinoma cells are of epithelial stem cell lineage (48), expressing Msi1 protein. Strong expression of the Msi1 protein has been observed in many tumors, such as glioma (25), hepatoma (26), colorectal adenoma (27,49), teratoid/rhabdoid tumors in eye (50), non-small cell lung cancer (51), retinoblastoma (52), medulloblastoma (53,54), ependymoma (53), endometrial carcinoma (55), neurocytoma (56), glioblastoma (57), cervical carcinoma (58), etc. Although the exact function of Msi1 in these cancer cells remains unclear, knockdown of Msi1 by using siRNA resulted in tumor growth arrest in colon adenocarcinoma xenografts transplanted in athymic nude mice, reduced cancer cell proliferation, and increased apoptosis (59).…”

Section: Msi1 and Diseasesmentioning

confidence: 99%

Notch Signaling in Hair Follicle Development

Bae¹,

Heon²,

이인호³

et al. 2017

Asian J Beauty Cosmetol

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The Musashi family is an evolutionarily conserved group of RNA-binding proteins. In mammal, two members of the group, Msi1 and Msi2, have been identified to date. Msi1 is considered to play roles in maintaining the stem cell status (stemness) of neural stem/progenitor cells in adults and in the development of central nervous system through translational regulation of its target mRNAs, which encode regulators of signal transduction and the cell cycle. Recently, strong expression of Msi1 in various somatic stem/progenitor cells of adult tissues, such as eye, gut, stomach, breast, and hair follicle, has been reported. The protein is also expressed in various cancer cells, and ectopically emerging cells have been found in neural tissues of patients with diseases involving neural disorder, including epilepsy. Many novel target mRNAs and regulatory pathways of Msi1 have been reported in recent years. Here, we present a review of the functions and action mechanisms of Msi1 protein and discuss possible directions for further study.

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Expression of the Neural RNA-Binding Protein Musashi1 in Pediatric Brain Tumors

Cited by 37 publications

References 39 publications

Expression of neural stem cell markers in malignant rhabdoid tumor cell lines

Expression of neural stem cell markers in malignant rhabdoid tumor cell lines

Analysis of stemness gene expression and CD133 abnormal methylation in neuroblastoma cell lines

Notch Signaling in Hair Follicle Development

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