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Melanie C MacNicol, Chad E Cragle, F Kennedy McDaniel, Linda L Hardy, Yan Wang, Karthik Arumugam, Yasir Rahmatallah, Galina V Glazko, Ania Wilczynska, Gwen V Childs, Daohong Zhou, Angus M MacNicol
The Musashi family of RNA binding proteins act to promote stem cell self-renewal and oppose cell differentiation predominantly through translational repression of mRNAs encoding pro-differentiation factors and inhibitors of cell cycle progression. During tissue development and repair however, Musashi repressor function must be dynamically regulated to allow cell cycle exit and differentiation. The mechanism by which Musashi repressor function is attenuated has not been fully established. Our prior work indicated that the Musashi1 isoform undergoes site-specific regulatory phosphorylation...
September 14, 2017: Scientific Reports
Ayuna Hattori, Makoto Tsunoda, Takaaki Konuma, Masayuki Kobayashi, Tamas Nagy, John Glushka, Fariba Tayyari, Daniel McSkimming, Natarajan Kannan, Arinobu Tojo, Arthur S Edison, Takahiro Ito
Reprogrammed cellular metabolism is a common characteristic observed in various cancers. However, whether metabolic changes directly regulate cancer development and progression remains poorly understood. Here we show that BCAT1, a cytosolic aminotransferase for branched-chain amino acids (BCAAs), is aberrantly activated and functionally required for chronic myeloid leukaemia (CML) in humans and in mouse models of CML. BCAT1 is upregulated during progression of CML and promotes BCAA production in leukaemia cells by aminating the branched-chain keto acids...
May 25, 2017: Nature
T Fujiwara, J Zhou, S Ye, H Zhao
The Musashi family of RNA-binding proteins, Musashi1 and Musashi2, regulate self-renewal and differentiation of neuronal and hematopoietic stem cells by modulating protein translation. It has been recently reported that Musashi2, not Musashi1, regulates hematopoietic stem cells. Although osteoclasts are derived from hematopoietic cells, the expression and functions of Musashi proteins in osteoclast lineage cells remain unknown. In this study, we have uncovered that Musashi2 is the predominant isoform of Musashi proteins in osteoclast precursors and its expression is upregulated by receptor activator of NF-κB ligand (RANKL) during osteoclast differentiation...
July 21, 2016: Cell Death & Disease
Tzu-Chieh Ho, James Taggart, Michael G Kharas
No abstract text is available yet for this article.
July 17, 2016: Cell Cycle
Weiwei Sheng, Ming Dong, Chuanping Chen, Yang Li, Qingfeng Liu, Qi Dong
Musashi2-Numb interaction plays a vital role in the progression of myeloid leukemia. However, its potential role in solid cancers has rarely been reported. We investigated the coordinate function of Musashi2-Numb in the development of pancreatic cancer (PC) in vitro and vivo. Both Musashi2 protein and mRNA levels were higher in PC tissues than that in paired normal pancreas (P<0.05). Musashi2 overexpression and Numb positive expression were positively and negatively associated with tumor size and UICC stage, respectively (P<0...
February 28, 2017: Oncotarget
Zhen Zong, Taicheng Zhou, Liangjun Rao, Zhipeng Jiang, Yingru Li, Zehui Hou, Bin Yang, Fanghai Han, Shuang Chen
Aberrant expression of musashi2 (MSI-2) has been detected in several malignancies. However, its role in the progression of colorectal cancer (CRC) remains unknown. Our study was designed to investigate the expression and prognostic significance of MSI-2 protein in patients with colorectal cancer. The expression of MSI-2 was detected in 164 patients' colorectal cancer and control specimens by the tissue microarray technique and immunohistochemical staining. The correlations between MSI-2 expression and clinicopathological variables including overall survival were analyzed...
April 2016: Cancer Medicine
Shasha Lu, Qitian Mu Mengxia Yu, Xiufeng Yin, Jian Chen, Jie Jin
No abstract text is available yet for this article.
July 7, 2015: Leukemia & Lymphoma
Sun-Mi Park, Mithat Gönen, Ly Vu, Gerard Minuesa, Patrick Tivnan, Trevor S Barlowe, James Taggart, Yuheng Lu, Raquel P Deering, Nir Hacohen, Maria E Figueroa, Elisabeth Paietta, Hugo F Fernandez, Martin S Tallman, Ari Melnick, Ross Levine, Christina Leslie, Christopher J Lengner, Michael G Kharas
Leukemia stem cells (LSCs) are found in most aggressive myeloid diseases and contribute to therapeutic resistance. Leukemia cells exhibit a dysregulated developmental program as the result of genetic and epigenetic alterations. Overexpression of the RNA-binding protein Musashi2 (MSI2) has been previously shown to predict poor survival in leukemia. Here, we demonstrated that conditional deletion of Msi2 in the hematopoietic compartment results in delayed leukemogenesis, reduced disease burden, and a loss of LSC function in a murine leukemia model...
March 2, 2015: Journal of Clinical Investigation
Ying Lu, Mengxia Yu, Qitian Mu, Renzhi Pei, Qiong Wang, Zhimei Chen, Jie Jin
OBJECTIVE: To explore the expression and clinical significance of Musashi2 (MSI2) gene in de novo acute myeloid leukemia (AML). METHODS: Real-time quantitative PCR (RQ-PCR) was used to measure the expression of MSI2 gene in 181 de novo AML patients. Correlation between the expression level and clinical features of such patients was explored. RESULTS: Transcript of the MSI2 gene was detected in 181 AML patients, with the median expression level being 2...
December 2014: Zhonghua Yi Xue Yi Chuan Xue za Zhi, Zhonghua Yixue Yichuanxue Zazhi, Chinese Journal of Medical Genetics
Danika Di Giacomo, Valentina Pierini, Gianluca Barba, Veronica Ceccarelli, Alba Vecchini, Cristina Mecucci
BACKGROUND: Musashi2(Msi2)-Numb pathway de-regulation is a molecular mechanism underlying the transition of chronic phase Ph + CML to deadly blast crisis, particularly in cases with a NUP98/HOXA9 fusion from a t(7;11)(p15;p15). This study provides new insights on the mechanisms cooperating in driving MSI2 over-expression and progression of Ph-positive CML. RESULTS: Herein we describe a t(7;11)(p15;p15) originating a NUP98 fusion with HOXA13, at 7p15, in a 39 year-old man in blast crisis of Ph-positive CML...
2014: Molecular Cytogenetics
Lu He, Xinke Zhou, Chen Qu, Lijuan Hu, Yunqiang Tang, Qiong Zhang, Min Liang, Jian Hong
The high incidence of recurrence and the poor prognosis of hepatocellular carcinoma (HCC) necessitate the discovery of new predictive markers of HCC invasion and prognosis. In this study, we evaluated the expression pattern of two members of a novel oncogene family, Musashi1 (MSI1) and Musashi2 (MSI2) in 40 normal hepatic tissue specimens, 149 HCC specimens and their adjacent non-tumourous tissues. We observed that MSI1 and MSI2 were significantly up-regulated in HCC tissues. High expression levels of MSI1 and MSI2 were detectable in 37...
January 2014: Journal of Cellular and Molecular Medicine
Huijuan Zhang, Shi Tan, Juan Wang, Shana Chen, Jing Quan, Jingrong Xian, Shuai shuai Zhang, Jingang He, Ling Zhang
The RNA-binding protein Musashi2 (Msi2) has been identified as a master regulator within a variety of stem cell populations via the regulation of translational gene expression. A recent study has suggested that Msi2 is strongly expressed in leukemic cells of acute myeloid leukemia patients, and elevated Msi2 is associated with poor prognosis. However, the potential role of Msi2 in leukemogenesis is still not well understood. Here, we investigated the effect of Msi2 knockdown on the biological properties of leukemic cells...
January 1, 2014: Experimental Cell Research
Modjtaba Emadi-Baygi, Parvaneh Nikpour, Faezeh Mohammad-Hashem, Mohamad Reza Maracy, Shaghayegh Haghjooy-Javanmard
Gastric cancer is the second most frequent cause of cancer death worldwide. In Iran, gastric cancer is the first cause of national cancer-related mortality in men and the second one in women. In mammals, the Musashi family of RNA binding proteins comprises the Musashi1 and Musashi2 proteins, encoded by the MSI1 and MSI2 genes. Mammalian Musashi contributes to the self-renewal of various types of stem cells. Furthermore, there is mounting evidence that stem cells exist in many tissues. Due to this, Msi appears to be associated with tumorigenesis...
November 2013: Pathology, Research and Practice
João Kleber Novais Pereira, Fabiola Traina, João Agostinho Machado-Neto, Adriana da Silva Santos Duarte, Matheus Rodrigues Lopes, Sara Teresinha Olalla Saad, Patricia Favaro
Recent studies have indicated the Musashi2/NUMB pathway as the key regulator of differentiation in chronic myeloid leukemia; however, a comparison of both gene expressions has not yet been made in myelodysplastic syndrome (MDS) and in acute myeloid leukemia (AML). We herein, demonstrate a statistically significant down-modulation of NUMB expression level in high-risk MDS and AML, compared with control individuals. MSI2 expression was significantly reduced in low and high-risk MDS compared with normal control samples...
October 2012: Leukemia Research
Erin L Wuebben, Sunil K Mallanna, Jesse L Cox, Angie Rizzino
Recent studies have shown that the RNA binding protein Musashi 2 (Msi2) plays important roles during development. Msi2 has also been shown to be elevated in several leukemias and its elevated expression has been linked with poorer prognosis in these cancers. Additionally, in embryonic stem cells (ESC) undergoing the early stages of differentiation, Msi2 has been shown to associate with the transcription factor Sox2, which is required for the self-renewal of ESC. These findings led us to examine the effects of Msi2 on the behavior of ESC...
2012: PloS One
Satoshi Kawase, Takao Imai, Chikako Miyauchi-Hara, Kunio Yaguchi, Yoshinori Nishimoto, Shin-ichi Fukami, Yumi Matsuzaki, Atsushi Miyawaki, Shigeyoshi Itohara, Hideyuki Okano
BACKGROUND: The specific genetic regulation of neural primordial cell determination is of great interest in stem cell biology. The Musashi1 (Msi1) protein, which belongs to an evolutionarily conserved family of RNA-binding proteins, is a marker for neural stem/progenitor cells (NS/PCs) in the embryonic and post-natal central nervous system (CNS). Msi1 regulates the translation of its downstream targets, including m-Numb and p21 mRNAs. In vitro experiments using knockout mice have shown that Msi1 and its isoform Musashi2 (Msi2) keep NS/PCs in an undifferentiated and proliferative state...
2011: Molecular Brain
Takahiro Ito, Hyog Young Kwon, Bryan Zimdahl, Kendra L Congdon, Jordan Blum, William E Lento, Chen Zhao, Anand Lagoo, Gareth Gerrard, Letizia Foroni, John Goldman, Harriet Goh, Soo-Hyun Kim, Dong-Wook Kim, Charles Chuah, Vivian G Oehler, Jerald P Radich, Craig T Jordan, Tannishtha Reya
Chronic myelogenous leukaemia (CML) can progress from a slow growing chronic phase to an aggressive blast crisis phase, but the molecular basis of this transition remains poorly understood. Here we have used mouse models of CML to show that disease progression is regulated by the Musashi-Numb signalling axis. Specifically, we find that the chronic phase is marked by high levels of Numb expression whereas the blast crisis phase has low levels of Numb expression, and that ectopic expression of Numb promotes differentiation and impairs advanced-phase disease in vivo...
August 5, 2010: Nature
D Sgubin, E Aztiria, A Perin, P Longatti, G Leanza
In the adult human brain, the presence of neural stem cells has been documented in the subgranular layer of the dentate gyrus of the hippocampus and in the subventricular zone of the lateral ventricles. Neurogenesis has also been reported in rodent models of ischemic stroke, traumatic brain injury, epileptic seizures, and intracerebral or subarachnoid hemorrhage. However, only sparse information is available about the occurrence of neurogenesis in the human brain under similar pathological conditions. In the present report, we describe neural progenitor cell proliferation in the brain of patients suffering from subarachnoid hemorrhage (SAH) resulting from ruptured aneurysm...
June 2007: Journal of Neuroscience Research
Jerome Aubert, Marios P Stavridis, Susan Tweedie, Michelle O'Reilly, Klemens Vierlinger, Meng Li, Peter Ghazal, Tom Pratt, John O Mason, Douglas Roy, Austin Smith
The transcription factor Sox1 is the earliest and most specific known marker for mammalian neural progenitors. During fetal development, Sox1 is expressed by proliferating progenitor cells throughout the central nervous system and in no tissue but the lens. We generated a reporter mouse line in which egfp is inserted into the Sox1 locus. Sox1GFP animals faithfully recapitulate the expression of the endogenous gene. We have used the GFP reporter to purify neuroepithelial cells by fluorescence-activated cell sorting from embryonic day 10...
September 30, 2003: Proceedings of the National Academy of Sciences of the United States of America
Shin-ichi Sakakibara, Yuki Nakamura, Tetsu Yoshida, Shinsuke Shibata, Masato Koike, Hiroshi Takano, Shuichi Ueda, Yasuo Uchiyama, Tetsuo Noda, Hideyuki Okano
Homologues of the Musashi family of RNA-binding proteins are evolutionarily conserved across species. In mammals, two members of this family, Musashi1 (Msi1) and Musashi2 (Msi2), are strongly coexpressed in neural precursor cells, including CNS stem cells. To address the in vivo roles of msi in neural development, we generated mice with a targeted disruption of the gene encoding Msi1. Homozygous newborn mice frequently developed obstructive hydrocephalus with aberrant proliferation of ependymal cells in a restricted area surrounding the Sylvius aqueduct...
November 12, 2002: Proceedings of the National Academy of Sciences of the United States of America
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