scholarly journals ZNF281 inhibits neuronal differentiation and is a prognostic marker for neuroblastoma

2018 ◽  
Vol 115 (28) ◽  
pp. 7356-7361 ◽  
Author(s):  
Marco Pieraccioli ◽  
Sara Nicolai ◽  
Consuelo Pitolli ◽  
Massimiliano Agostini ◽  
Alexey Antonov ◽  
...  
Keyword(s):  
Neuronal Differentiation ◽  
Prognostic Marker ◽  
Cortical Neurons ◽  
Ectopic Expression ◽  
Bioinformatic Analysis ◽  
Cellular Processes ◽  
Stage 4 ◽  
Stage 1 ◽  
Inappropriate Expression

Derangement of cellular differentiation because of mutation or inappropriate expression of specific genes is a common feature in tumors. Here, we show that the expression of ZNF281, a zinc finger factor involved in several cellular processes, decreases during terminal differentiation of murine cortical neurons and in retinoic acid-induced differentiation of neuroblastoma (NB) cells. The ectopic expression of ZNF281 inhibits the neuronal differentiation of murine cortical neurons and NB cells, whereas its silencing causes the opposite effect. Furthermore, TAp73 inhibits the expression of ZNF281 through miR34a. Conversely, MYCN promotes the expression of ZNF281 at least in part by inhibiting miR34a. These findings imply a functional network that includes p73, MYCN, and ZNF281 in NB cells, where ZNF281 acts by negatively affecting neuronal differentiation. Array analysis of NB cells silenced for ZNF281 expression identified GDNF and NRP2 as two transcriptional targets inhibited by ZNF281. Binding of ZNF281 to the promoters of these genes suggests a direct mechanism of repression. Bioinformatic analysis of NB datasets indicates that ZNF281 expression is higher in aggressive, undifferentiated stage 4 than in localized stage 1 tumors supporting a central role of ZNF281 in affecting the differentiation of NB. Furthermore, patients with NB with high expression of ZNF281 have a poor clinical outcome compared with low-expressors. These observations suggest that ZNF281 is a controller of neuronal differentiation that should be evaluated as a prognostic marker in NB.

scholarly journals Ischemic Cerebral Endothelial Cell–Derived Exosomes Promote Axonal Growth

Stroke ◽  
2020 ◽  
Vol 51 (12) ◽  
pp. 3701-3712
Author(s):  
Yi Zhang ◽  
Yi Qin ◽  
Michael Chopp ◽  
Chao Li ◽  
Amy Kemper ◽  
...  
Keyword(s):  
Cortical Neurons ◽  
Neuronal Cell ◽  
Axonal Growth ◽  
Mature Mirnas ◽  
Bioinformatic Analysis ◽  
Axonal Outgrowth ◽  
Ischemic Brain ◽  
Neuronal Homeostasis ◽  
Neuronal Cell Bodies

Background and Purpose: Cerebral endothelial cells (CECs) and axons of neurons interact to maintain vascular and neuronal homeostasis and axonal remodeling in normal and ischemic brain, respectively. However, the role of exosomes in the interaction of CECs and axons in brain under normal conditions and after stroke is unknown. Methods: Exosomes were isolated from CECs of nonischemic rats and is chemic rats (nCEC-exos and isCEC-exos), respectively. A multicompartmental cell culture system was used to separate axons from neuronal cell bodies. Results: Axonal application of nCEC-exos promotes axonal growth of cortical neurons, whereas isCEC-exos further enhance axonal growth than nCEC-exos. Ultrastructural analysis revealed that CEC-exos applied into distal axons were internalized by axons and reached to their parent somata. Bioinformatic analysis revealed that both nCEC-exos and isCEC-exos contain abundant mature miRNAs; however, isCEC-exos exhibit more robust elevation of select miRNAs than nCEC-exos. Mechanistically, axonal application of nCEC-exos and isCEC-exos significantly elevated miRNAs and reduced proteins in distal axons and their parent somata that are involved in inhibiting axonal outgrowth. Blockage of axonal transport suppressed isCEC-exo–altered miRNAs and proteins in somata but not in distal axons. Conclusions: nCEC-exos and isCEC-exos facilitate axonal growth by altering miRNAs and their target protein profiles in recipient neurons.

scholarly journals A role for neural determination genes in specifying the dorsoventral identity of telencephalic neurons

2000 ◽  
Vol 14 (1) ◽  
pp. 67-80 ◽  
Author(s):  
Carol Fode ◽  
Qiufu Ma ◽  
Simona Casarosa ◽  
Siew-Lan Ang ◽  
David J. Anderson ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Cortical Neurons ◽  
Double Mutant ◽  
Ectopic Expression ◽  
Neuronal Identity ◽  
Dorsal Telencephalon ◽  
Bhlh Transcription Factors ◽  
Type Specification ◽  
Neuronal Type

Neurogenin1 (Ngn1), Neurogenin2(Ngn2), and Mash1 encode bHLH transcription factors with neuronal determination functions. In the telencephalon, theNgns and Mash1 are expressed at high levels in complementary dorsal and ventral domains, respectively. We found thatNgn function is required to maintain these two separate expression domains, as Mash1 expression is up-regulated in the dorsal telencephalon of Ngn mutant embryos. We have taken advantage of the replacement of the Ngns by Mash1 in dorsal progenitors to address the role of the neural determination genes in neuronal-type specification in the telencephalon. InNgn2 single and Ngn1; Ngn2 double mutants, a population of early born cortical neurons lose expression of dorsal-specific markers and ectopically express a subset of ventral telencephalic-specific markers. Analysis of Mash1; Ngn2double mutant embryos and of embryos carrying a Ngn2 toMash1 replacement mutation demonstrated that ectopic expression of Mash1 is required and sufficient to confer these ventral characteristics to cortical neurons. Our results indicate that in addition to acting as neuronal determinants, Mash1 andNgns play a role in the specification of dorsal-ventral neuronal identity, directly linking pathways of neurogenesis and regional patterning in the forebrain.

scholarly journals MicroRNA-125b Promotes Neuronal Differentiation in Human Cells by Repressing Multiple Targets

2009 ◽  
Vol 29 (19) ◽  
pp. 5290-5305 ◽  
Author(s):  
Minh T. N. Le ◽  
Huangming Xie ◽  
Beiyan Zhou ◽  
Poh Hui Chia ◽  
Pamela Rizk ◽  
...  
Keyword(s):  
Gene Expression ◽  
Neurite Outgrowth ◽  
Neuronal Differentiation ◽  
Neural Development ◽  
Ectopic Expression ◽  
Global Changes ◽  
Human Neuroblastoma Cell ◽  
Human Neuroblastoma ◽  
Mrna Targets

ABSTRACT MicroRNAs (miRNAs) are a class of small noncoding RNAs that regulate gene expression at the posttranscriptional level. Research on miRNAs has highlighted their importance in neural development, but the specific functions of neurally enriched miRNAs remain poorly understood. We report here the expression profile of miRNAs during neuronal differentiation in the human neuroblastoma cell line SH-SY5Y. Six miRNAs were significantly upregulated during differentiation induced by all-trans-retinoic acid and brain-derived neurotrophic factor. We demonstrated that the ectopic expression of either miR-124a or miR-125b increases the percentage of differentiated SH-SY5Y cells with neurite outgrowth. Subsequently, we focused our functional analysis on miR-125b and demonstrated the important role of this miRNA in both the spontaneous and induced differentiations of SH-SH5Y cells. miR-125b is also upregulated during the differentiation of human neural progenitor ReNcell VM cells, and miR-125b ectopic expression significantly promotes the neurite outgrowth of these cells. To identify the targets of miR-125b regulation, we profiled the global changes in gene expression following miR-125b ectopic expression in SH-SY5Y cells. miR-125b represses 164 genes that contain the seed match sequence of the miRNA and/or that are predicted to be direct targets of miR-125b by conventional methods. Pathway analysis suggests that a subset of miR-125b-repressed targets antagonizes neuronal genes in several neurogenic pathways, thereby mediating the positive effect of miR-125b on neuronal differentiation. We have further validated the binding of miR-125b to the miRNA response elements of 10 selected mRNA targets. Together, we report here for the first time the important role of miR-125b in human neuronal differentiation.

scholarly journals NACC-1 regulates hepatocellular carcinoma cell malignancy and is targeted by miR-760

2020 ◽  
Vol 52 (3) ◽  
pp. 302-309
Author(s):  
Linan Yin ◽  
Tingting Sun ◽  
Ruibao Liu
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Lines ◽  
Bioinformatic Analysis ◽  
Cellular Growth ◽  
Luciferase Assay ◽  
Migration And Invasion ◽  
Cellular Processes ◽  
Therapeutic Benefits ◽  
The Impact

Abstract Hepatocellular carcinoma (HCC) is the most prominent form of presentation in liver cancer. It is also the fourth most common cause of cancer-associated deaths globally. The role of nucleus accumbens associated protein-1 (NACC-1) has been evaluated in several cancers. This protein is a transcriptional regulator that regulates a number of significant cellular processes. In the current study, we aimed to understand the role of NACC-1 in HCC. Primarily, we measured the expression of NACC-1 using quantitative real time polymerase chain reaction and western blot analysis. We knocked down the expression of NACC-1 in HCC cell lines Huh7 and HepG2 by transferring a commercially synthesized small interfering RNA and explored the impact of NACC-1 knockdown on cellular growth, migration, invasion, and chemoresistance to doxorubicin. Through bioinformatic analysis, we identified NACC-1 as a potential target of miR-760. Using a dual reporter luciferase assay, we confirmed the predicted target and assessed miR-760-mediated regulation of NACC-1 and rescue of tumorigenic phenotypes. We observed increased expression of NACC-1 in HCC. Furthermore, knockdown of NACC-1 resulted in reduced cell proliferation and invasion and increased susceptibility to doxorubicin-mediated chemosensitivity. Overexpression of miR-760 in HCC cell lines rescued NACC-1-mediated migration and invasion. We revealed that miR-760 regulated NACC-1 expression in HCC. Our data indicated that both miR-760 and NACC-1 could be used as prognostic markers, and miR-760 may have therapeutic benefits for HCC and other cancers.

scholarly journals UNC-45A is required for neurite extension via controlling NMII activation

2017 ◽  
Vol 28 (10) ◽  
pp. 1337-1346 ◽  
Author(s):  
Yoshie Iizuka ◽  
Ashley Mooneyham ◽  
Andrew Sieben ◽  
Kevin Chen ◽  
Makayla Maile ◽  
...  
Keyword(s):  
Neuronal Differentiation ◽  
Growth Cone ◽  
Molecular Mechanisms ◽  
Neurite Growth ◽  
Multiprotein Complex ◽  
Master Regulator ◽  
Neurite Extension ◽  
Cellular Processes ◽  
Neurite Elongation

UNC-45A is a highly conserved member of the UNC-45/CRO1/She4p family of proteins, which act as chaperones for conventional and nonconventional myosins. NMII mediates contractility and actin-based motility, which are fundamental for proper growth cone motility and neurite extension. The presence and role of UNC-45A in neuronal differentiation have been largely unknown. Here we demonstrate that UNC-45A is a novel growth cone–­localized, NMII-associated component of the multiprotein complex regulating growth cone dynamics. We show that UNC-45A is dispensable for neuron survival but required for neurite elongation. Mechanistically, loss of UNC-45A results in increased levels of NMII activation. Collectively our results provide novel insights into the molecular mechanisms of neurite growth and define UNC-45A as a novel and master regulator of NMII-mediated cellular processes in neurons.

scholarly journals The Role of Histone Lysine Methylation in the Response of Mammalian Cells to Ionizing Radiation

2021 ◽  
Vol 12 ◽  
Author(s):  
Elena Di Nisio ◽  
Giuseppe Lupo ◽  
Valerio Licursi ◽  
Rodolfo Negri
Keyword(s):  
Cell Lines ◽  
Protein Interactions ◽  
Mammalian Cells ◽  
Bioinformatic Analysis ◽  
Mrna Levels ◽  
Lysine Methylation ◽  
Histone Lysine Methylation ◽  
Cellular Processes ◽  
Histone Lysine

Eukaryotic genomes are wrapped around nucleosomes and organized into different levels of chromatin structure. Chromatin organization has a crucial role in regulating all cellular processes involving DNA-protein interactions, such as DNA transcription, replication, recombination and repair. Histone post-translational modifications (HPTMs) have a prominent role in chromatin regulation, acting as a sophisticated molecular code, which is interpreted by HPTM-specific effectors. Here, we review the role of histone lysine methylation changes in regulating the response to radiation-induced genotoxic damage in mammalian cells. We also discuss the role of histone methyltransferases (HMTs) and histone demethylases (HDMs) and the effects of the modulation of their expression and/or the pharmacological inhibition of their activity on the radio-sensitivity of different cell lines. Finally, we provide a bioinformatic analysis of published datasets showing how the mRNA levels of known HMTs and HDMs are modulated in different cell lines by exposure to different irradiation conditions.

Alterations in the number of motoneurons containing immunoreactive calcitonin gene-related peptide(CGRP)& choline acetyltransferase(ChAT) in the cervical spinal cord of the wobbler mouse during the development of the motoneuron disease

1995 ◽  
Vol 53 ◽  
pp. 970-971
Author(s):  
L. Vacca-Galloway ◽  
Y.Q. Zhang ◽  
P. Bose ◽  
S.H. Zhang
Keyword(s):  
Spinal Cord ◽  
Early Stage ◽  
Cervical Spinal Cord ◽  
Wild Type Mouse ◽  
Reflex Response ◽  
Mouse Strains ◽  
Behavioral Tests ◽  
Wobbler Mouse ◽  
Stage 4 ◽  
Stage 1

The Wobbler mouse (wr) has been studied as a model for inherited human motoneuron diseases (MNDs). Using behavioral tests for forelimb power, walking, climbing, and the “clasp-like reflex” response, the progress of the MND can be categorized into early (Stage 1, age 21 days) and late (Stage 4, age 3 months) stages. Age-and sex-matched normal phenotype littermates (NFR/wr) were used as controls (Stage 0), as well as mice from two related wild-type mouse strains: NFR/N and a C57BI/6N. Using behavioral tests, we also detected pre-symptomatic Wobblers at postnatal ages 7 and 14 days. The mice were anesthetized and perfusion-fixed for immunocytochemical (ICC) of CGRP and ChAT in the spinal cord (C3 to C5).Using computerized morphomety (Vidas, Zeiss), the numbers of IR-CGRP labelled motoneurons were significantly lower in 14 day old Wobbler specimens compared with the controls (Fig. 1). The same trend was observed at 21 days (Stage 1) and 3 months (Stage 4). The IR-CGRP-containing motoneurons in the Wobbler specimens declined progressively with age.

Dysregulation of HOX as a Potential Therapeutic Target in Breast Cancer

2020 ◽  
Vol 27 ◽  
Author(s):  
Ji-Yeon Lee ◽  
Myoung Hee Kim
Keyword(s):  
Breast Cancer ◽  
Hox Genes ◽  
Therapeutic Potential ◽  
Expression Patterns ◽  
Genome Structure ◽  
Control Cell ◽  
Three Dimensional ◽  
Cellular Processes ◽  
Hox Protein

: HOX genes belong to the highly conserved homeobox superfamily, responsible for the regulation of various cellular processes that control cell homeostasis, from embryogenesis to carcinogenesis. The abnormal expression of HOX genes is observed in various cancers, including breast cancer; they act as oncogenes or as suppressors of cancer, according to context. In this review, we analyze HOX gene expression patterns in breast cancer and examine their relationship, based on the three-dimensional genome structure of the HOX locus. The presence of non-coding RNAs, embedded within the HOX cluster, and the role of these molecules in breast cancer have been reviewed. We further evaluate the characteristic activity of HOX protein in breast cancer and its therapeutic potential.

MiRNA-145 and Its Direct Downstream Targets in Digestive System Cancers: A Promising Therapeutic Target

2020 ◽  
Vol 26 ◽  
Author(s):  
Yini Ma ◽  
Xiu Cao ◽  
Guojuan Shi ◽  
Tianlu Shi
Keyword(s):  
Digestive System ◽  
Target Genes ◽  
Malignant Neoplasm ◽  
Vital Role ◽  
Diagnostic Biomarkers ◽  
Cellular Processes ◽  
Promising Therapeutic Target ◽  
Direct Target ◽  
Potential Strategy

: MicroRNAs (miRNAs) play a vital role in the onset and development of many diseases, including cancers. Emerging evidence shows that numerous miRNAs have the potential to be used as diagnostic biomarkers for cancers, and miRNA-based therapy may be a promising therapy for the treatment of malignant neoplasm. MicroRNA-145 (miR-145) has been considered to play certain roles in various cellular processes, such as proliferation, differentiation and apoptosis, via modulating expression of direct target genes. Recent reports show that miR-145 participates in the progression of digestive system cancers, and plays crucial and novel roles for cancer treatment. In this review, we summarize the recent knowledge concerning the function of miR-145 and its direct targets in digestive system cancers. We discuss the potential role of miR-145 as valuable biomarkers for digestive system cancers and how miR-145 regulates these digestive system cancers via different targets to explore the potential strategy of targeting miR-145.

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