An Alu‐like RNA promotes cell differentiation and reduces malignancy of human neuroblastoma cells

Castelnuovo, Manuele; Massone, Sara; Tasso, Roberta; Fiorino, Gloria; Gatti, Monica; Robello, Mauro; Gatta, Elena; Berger, Audrey; Strub, Katharina; Florio, Tullio; Dieci, Giorgio; Cancedda, Ranieri; Pagano, Aldo

doi:10.1096/fj.10-157032

Cited by 69 publications

(85 citation statements)

References 22 publications

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“…This Alu-like RNA is transcribed by RNA polymerase III from the first intron of the ASCL3 (Achaete ScuteLike homologue 3) gene. Stable overexpression of NDM29 in a MYCN-amplified neuroblastoma cell line induced neuronal differentiation, reduced the proliferation rate, reduced c-kit expression, induced anchorage-dependent growth, and decreased anticancer drug resistance through MDR1 (multidrug resistance 1) downregulation (90). Although the status of N-myc expression was not reported in these experiments, it is interesting to notice that NDM29 overexpression coincides the effects of MYCN knockdown in MYCN-amplified neuroblastoma cells (91)(92)(93).…”

Section: N-myc Alters Expression Of Other Noncoding Rnasmentioning

confidence: 81%

N-myc and Noncoding RNAs in Neuroblastoma

Buechner

Einvik

2012

Molecular Cancer Research

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Neuroblastoma is a pediatric tumor of the sympathetic nervous system. Amplification and overexpression of the MYCN proto-oncogene occurs in approximately 20% of neuroblastomas and is associated with advanced stage disease, rapid tumor progression, and poor prognosis. MYCN encodes the transcriptional regulator N-myc, which has been shown to both up-and downregulate many target genes involved in cell cycle, DNA damage, differentiation, and apoptosis in neuroblastoma. During the last years, it has become clear that N-myc also modulates the expression of several classes of noncoding RNAs, in particular microRNAs. MicroRNAs are the most widely studied noncoding RNA molecules in neuroblastoma. They function as negative regulators of gene expression at the posttranscriptional level in diverse cellular processes. Aberrant regulation of miRNA expression has been implicated in the pathogenesis of neuroblastoma. While the N-myc protein is established as an important regulator of several miRNAs involved in neuroblastoma tumorigenesis, tumor suppressor miRNAs have also been documented to repress MYCN expression and inhibit cell proliferation of MYCN-amplified neuroblastoma cells.

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Section: N-myc Alters Expression Of Other Noncoding Rnasmentioning

confidence: 81%

N-myc and Noncoding RNAs in Neuroblastoma

Buechner

Einvik

2012

Molecular Cancer Research

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“…This cell line tool was appropriate not only to highlight the effects of anti-21A RNAs transfection on the proliferation of more mature cells, but also to identify possible effects on the cell differentiation status. 13,21 First, we tested the kinetics of decay of an equimolar mixture (2 £ 10 ¡3 picomols/cell) of a, b and g anti-21A RNAs (hereafter referred to as anti-21A RNAs mix) in the cells. Given their increased stability, orthomethylated RNA molecules were chosen to exert prolonged effects, but not long enough to lead to a permanent perturbation of the gene expression profile of the transfected cells.…”

Section: Resultsmentioning

confidence: 99%

“…2 In the recent years we defined the transcriptional role of several of these ncRNA. [13][14][15][16][17][18][19] While investigating the biological role of one of these transcription units (named 21A), we documented an inverse correlation between the expression level of 21A ncRNA and the rate of cell proliferation. 2 Indeed, the transfection of cells with a construct expressing 21A ncRNA in antisense configuration led to a marked increase of cell proliferation.…”

Section: Introductionmentioning

confidence: 91%

Down-regulation of 21A Alu RNA as a tool to boost proliferation maintaining the tissue regeneration potential of progenitor cells

et al. 2016

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ABSTRACT21A is an Alu non-coding (nc) RNA transcribed by RNA polymerase (pol) III. While investigating the biological role of 21A ncRNA we documented an inverse correlation between its expression level and the rate of cell proliferation. The downregulation of this ncRNA not only caused a boost in cell proliferation, but was also associated to a transient cell dedifferentiation, suggesting a possible involvement of this RNA in cell dedifferentiation/reprogramming. In this study, we explored the possibility to enhance proliferation and dedifferentiation of cells of interest, by 21A down-regulation, using a mixture of chemically modified Anti-21A RNAs. Our results confirmed the validity of this approach that allows the amplification of specific cell populations, in a controlled manner and without inducing permanent effects. In addition to induce cell proliferation, the procedure did not decrease the tissue regeneration potential of progenitor cells in two different cell systems.

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“…Many other ncRNAs including Alu RNA [75], Y RNA [76], and small nucleolar RNA [77], show abnormal expression patterns in cancerous tissues. Their roles and possible mechanisms are not reviewed here; however, some details about them are described in the references.…”

Section: Other Ncrnasmentioning

confidence: 99%

Noncoding RNAs: Different roles in tumorigenesis

Lin

2012

Chin. Sci. Bull.

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A major portion of the mammalian genome is transcribed to produce large numbers of noncoding RNAs (ncRNAs). During the past decade, the discovery of small RNAs, including the microRNAs (miRNA) and small interfering RNAs (siRNA), has led to important advances in biology. The breadth of the ncRNA field of study has substantially expanded and many recent results have revealed a range of functions that can be attributed to the miRNAs and other ncRNAs. For example, H19 RNA, HOTAIR RNA, transcribed ultraconserved regions (T-UCRs), natural antisense RNA, transfer RNA and mitochondrial noncoding RNA have been suggested to play important roles in cancers and other diseases as well as in diverse cellular processes. In this review, we focus on the current status of several classes of ncRNAs associated with cancer with the emphasis on those that are not microRNAs. Mounting evidence has revealed that a major portion of the mammalian genome is transcribed to produce large numbers of noncoding RNAs (ncRNAs), that is, RNAs that either do not have an open reading frame or RNAs that have a short poorly conserved open reading frame and do not code for a protein [1,2]. During the past decade, the discovery of small RNAs including the microRNAs (miRNAs) and small interfering RNAs (siRNAs) has led to major advances in biology. After miRNAs were first connected to cancer pathogenesis [3], accumulating data have pointed to a central regulatory role for miRNAs in the initiation and progression of most of the cancers that have been analyzed so far. Recently, the breadth of the ncRNA field of study has substantially expanded. A series of studies have revealed the essential roles of many ncRNAs in diverse cellular processes including cancer; these ncRNAs include H19 RNA, HOTAIR RNA, transcribed ultraconserved regions (T-UCRs), natural antisense RNA, transfer RNA and mitochondrial noncoding RNA (Figure 1). In this review, we focus on the current status of the research into the several classes of ncRNAs associated with cancer.

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An Alu‐like RNA promotes cell differentiation and reduces malignancy of human neuroblastoma cells

Cited by 69 publications

References 22 publications

N-myc and Noncoding RNAs in Neuroblastoma

N-myc and Noncoding RNAs in Neuroblastoma

Down-regulation of 21A Alu RNA as a tool to boost proliferation maintaining the tissue regeneration potential of progenitor cells

Noncoding RNAs: Different roles in tumorigenesis

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