An integrative genomics screen uncovers ncRNA T-UCR functions in neuroblastoma tumours

Mestdagh, Pieter; Fredlund, Erik; Pattyn, Filip; Rihani, Ali; Maerken, Tom Van; Vermeulen, Joëlle; Kumps, Candy; Menten, Björn; Preter, Katleen De; Schramm, Alexander; Schulte, Johannes H.; Noguera, Rosa; Schleiermacher, Gudrun; Janoueix‐Lerosey, Isabelle; Laureys, Geneviève; Powel, R.; Nittner, David; Marine, Jean–Christophe; Ringnér, Markus; Speleman, Frank; Vandesompele, Jo

doi:10.1038/onc.2010.106

Cited by 138 publications

(142 citation statements)

References 32 publications

(50 reference statements)

Supporting

Mentioning

132

Contrasting

Unclassified

Order By: Relevance

“…Of these 7, 3 (uc.350, uc.379, and uc.460) were also upregulated when Nmyc expression was induced in the SHEP-MYCN-ER cell line, supporting that these T-UCRs are N-myc responsive. These data indicate that differential T-UCR expression correlates with clinicogenetic parameters such as MYCN amplification (85).…”

Section: N-myc Alters Expression Of Other Noncoding Rnasmentioning

confidence: 72%

“…TUCRs are widely expressed in neuroblastoma, and a signature based on the expression of 28 T-UCRs has been shown to be associated with good outcome in noninfant patients with metastatic disease (84). Furthermore, Mestdagh and colleagues (85) investigated the global T-UCR expression in neuroblastoma and found a signature of 7 T-UCRs significantly upregulated in MYCN-amplified tumors (n ¼ 18) compared with nonamplified tumors (n ¼ 31). Of these 7, 3 (uc.350, uc.379, and uc.460) were also upregulated when Nmyc expression was induced in the SHEP-MYCN-ER cell line, supporting that these T-UCRs are N-myc responsive.…”

Section: N-myc Alters Expression Of Other Noncoding Rnasmentioning

confidence: 99%

See 1 more Smart Citation

N-myc and Noncoding RNAs in Neuroblastoma

Buechner

Einvik

2012

Molecular Cancer Research

View full text Add to dashboard Cite

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.

show abstract

Section: N-myc Alters Expression Of Other Noncoding Rnasmentioning

confidence: 72%

Section: N-myc Alters Expression Of Other Noncoding Rnasmentioning

confidence: 99%

N-myc and Noncoding RNAs in Neuroblastoma

Buechner

Einvik

2012

Molecular Cancer Research

View full text Add to dashboard Cite

show abstract

“…Functional annotation analysis identified the top four significantly overrepresented cellular process gene classifications (and number of genes) as transcription (569), cell cycle (248), ubiquitin cycle (225), and cell division (115), whereas the top four overrepresented molecular function classifications were ligase activity (159), protein binding (1,810), nucleotide binding (774), and ATP binding (638). The top four significantly overrepresented GenMAPP pathway gene classifications were cell cycle/KEGG (56), mRNA processing reactome (63), RNA transcription reactome (28), and G1 to S cellcycle reactome (41). These data suggested that TUC338 could modulate cellular processes involved in cell growth.…”

mentioning

confidence: 82%

“…The ultraconserved element 73 (uc.73), for example, modulates apoptosis and cell proliferation in colorectal cancer cells (26). A correlation of some ucRNA with clinical prognostic factors, such as Myc amplification, has been reported in neuroblastoma (28). Although rare, single-nucleotide polymorphisms in ultraconserved regions have been reported in familial breast cancer, chronic lymphocytic leukemia, and colorectal cancer (29,30).…”

mentioning

confidence: 99%

Expression and functional role of a transcribed noncoding RNA with an ultraconserved element in hepatocellular carcinoma

Braconi¹,

Valeri²,

Kogure³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

201

164

View full text Add to dashboard Cite

Although expression of non-protein-coding RNA (ncRNA) can be altered in human cancers, their functional relevance is unknown. Ultraconserved regions are noncoding genomic segments that are 100% conserved across humans, mice, and rats. Conservation of gene sequences across species may indicate an essential functional role, and therefore we evaluated the expression of ultraconserved RNAs (ucRNA) in hepatocellular cancer (HCC). The global expression of ucRNAs was analyzed with a custom microarray. Expression was verified in cell lines by real-time PCR or in tissues by in situ hybridization using tissue microarrays. Cellular ucRNA expression was modulated with siRNAs, and the effects on global gene expression and growth of human and murine HCC cells were evaluated. Fifty-six ucRNAs were aberrantly expressed in HepG2 cells compared with nonmalignant hepatocytes. Among these ucRNAs, the greatest change was noted for ultraconserved element 338 (uc.338), which was dramatically increased in human HCC compared with noncancerous adjacent tissues. Although uc.338 is partially located within the poly(rC) binding protein 2 (PCBP2) gene, the transcribed ncRNA encoding uc.338 is expressed independently of PCBP2 and was cloned as a 590-bp RNA gene, termed TUC338. Functional gene annotation analysis indicated predominant effects on genes involved in cell growth. These effects were experimentally demonstrated in both human and murine cells. siRNA to TUC338 decreased both anchorage-dependent and anchorage-independent growth of HCC cells. These studies identify a critical role for TUC338 in regulation of transformed cell growth and of transcribed ultraconserved ncRNA as a unique class of genes involved in the pathobiology of HCC.liver cancer | hepatocarcinoma | exaptation | transposon

show abstract

“…UCRs regulate the expression and translation of mRNAs. By regulating protein production post-transcriptionally, a number of UCRs act as oncogenes or tumor suppressor genes (6)(7)(8)12,13). However, the regulation of TUC338 and its underlying molecular mechanisms of action in CC are unknown.…”

Section: Discussionmentioning

confidence: 99%

TUC338 promotes cell migration and invasion by targeting TIMP1 in cervical cancer

2017

View full text Add to dashboard Cite

Abstract. Ultraconserved regions (UCRs) are non-proteincoding gene sequences that are strictly conserved across numerous distinct species. It has been demonstrated previously that UCRs encoding non-coding RNAs serve as regulators of gene expression. In recent decades, there has been increasing evidence for the involvement of UCRs in carcinogenesis. In previous studies, the non-coding RNA transcribed ultraconserved element 338 (TUC338) was identified to serve an oncogenic role in hepatocellular cancer; however, thus far, the role of TUC338 in cervical cancer (CC) remains undefined. The results of the present study revealed that TUC338 is significantly upregulated in CC tissues and cell lines, and that the upregulation of TUC338 is associated with lymph node metastasis. Transfection with small interfering RNA (siRNA) against TUC338 could markedly inhibit cell migration and invasion in HeLa and C33A CC cell lines. Using a dual-luciferase reporter assay, tissue inhibitor of metalloproteinase 1 (TIMP1) was demonstrated to be negatively regulated by TUC338 at the post-transcriptional level, via a specific target site within the 3' untranslated region. The expression of TIMP1 was also observed to be inversely associated with TUC338 expression in CC tissues. Overexpression of TIMP1 with MigRI-TIMP1-green fluorescent protein inhibited CC cell migration and invasion and downregulated matrix metalloproteinase 9, resembling the effects of TUC338 siRNA. Therefore, the results of the present study suggest that TUC338 acts as a novel oncogene by targeting the TIMP1 gene, and inhibiting CC cell migration and invasion.

show abstract

An integrative genomics screen uncovers ncRNA T-UCR functions in neuroblastoma tumours

Cited by 138 publications

References 32 publications

N-myc and Noncoding RNAs in Neuroblastoma

N-myc and Noncoding RNAs in Neuroblastoma

Expression and functional role of a transcribed noncoding RNA with an ultraconserved element in hepatocellular carcinoma

TUC338 promotes cell migration and invasion by targeting TIMP1 in cervical cancer

Contact Info

Product

Resources

About