Early Targets of miR-34a in Neuroblastoma

Antonellis, Pasqualino De; Carotenuto, Marianeve; Vandenbussche, Jonathan; Vita, Gennaro De; Ferrucci, Veronica; Medaglia, Chiara; Boffa, Iolanda; Galiero, Alessandra; Somma, Sarah Di; Magliulo, Daniela; Aiese, Nadia; Alonzi, Alessandro; Spano, Daniela; Liguori, Lucia; Chiarolla, Cristina M.; Verrico, Antonio; Schulte, Johannes H.; Mestdagh, Pieter; Vandesompele, Jo; Gevaert, Kris; Zollo, Massimo

doi:10.1074/mcp.m113.035808

Cited by 32 publications

(23 citation statements)

References 75 publications

(88 reference statements)

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“…17, 29, 30, 31 It directly regulates the expression of proteins involved in cell cycle, differentiation, apoptosis, and antagonizes processes. 32, 33 We reveal a role of miRNA-34a in hepatoblastoma progression.…”

Section: Discussionmentioning

confidence: 99%

Targeting long non-coding RNA-TUG1 inhibits tumor growth and angiogenesis in hepatoblastoma

et al. 2016

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Hepatoblastoma is the most common liver tumor of early childhood, which is usually characterized by unusual hypervascularity. Recently, long non-coding RNAs (lncRNA) have emerged as gene regulators and prognostic markers in several cancers, including hepatoblastoma. We previously reveal that lnRNA-TUG1 is upregulated in hepatoblastoma specimens by microarray analysis. In this study, we aim to elucidate the biological and clinical significance of TUG1 upregulation in hepatoblastoma. We show that TUG1 is significantly upregulated in human hepatoblastoma specimens and metastatic hepatoblastoma cell lines. TUG1 knockdown inhibits tumor growth and angiogenesis in vivo, and decreases hepatoblastoma cell viability, proliferation, migration, and invasion in vitro. TUG1, miR-34a-5p, and VEGFA constitutes to a regulatory network, and participates in regulating hepatoblastoma cell function, tumor progression, and tumor angiogenesis. Overall, our findings indicate that TUG1 upregulation contributes to unusual hypervascularity of hepatoblastoma. TUG1 is a promising therapeutic target for aggressive, recurrent, or metastatic hepatoblastoma.

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Section: Discussionmentioning

confidence: 99%

Targeting long non-coding RNA-TUG1 inhibits tumor growth and angiogenesis in hepatoblastoma

et al. 2016

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“…In NIH-3T3 cells, LYAR overexpression was also found to promote cell proliferation [ 9 ]. In neuroblastoma, LYAR was one gene product that correlated with worse clinical outcomes [ 17 ]. However, analysis of the whole-genome expression profile of blood cells in ovarian cancer patients showed that LYAR was one of six genes that were significantly down-regulated in the poor prognosis group [ 11 ].…”

Section: Discussionmentioning

confidence: 99%

LYAR promotes colorectal cancer cell mobility by activating galectin-1 expression

Liu

et al. 2015

Oncotarget

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Colorectal cancer (CRC) is one of the leading causes of cancer-related death worldwide. However, the molecular mechanisms of CRC pathogenesis are not fully understood. In this study, we report the characterization of LYAR (Ly-1 antibody reactive clone) as a key regulator of the migration and invasion of human CRC cells. Immunohistochemistry analysis demonstrated that LYAR is expressed at a higher level in metastatic CRC tissues. We found that LYAR promoted the migratory and invasive capabilities of CRC cells. Gene expression profile analysis of CRC cells showed that LGALS1, which encodes the galectin-1 protein, was a potential target of LYAR. The ChIP assay and gene reporter assays indicated that LYAR directly bound to the LGALS1 promoter. The ectopic expression of galectin-1 partially restored the mobile potential of LYAR knocked-down cells, which suggests that galectin-1 contributed to the LYAR-promoted cell migration and invasion of CRC cells. Thus, this study revealed a novel mechanism by which the transcription factor LYAR may promote tumor cell migration and invasion by upregulating galectin-1 gene expression in CRC.

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“…20,21 The TF CCCTC-binding factor (CTCF) is also a validated target of miR-34a based on reporter assays showing that miR-34a represses CTCF expression. 22 Finally, protein expression of N-Myc was inversely correlated to miR-34 in miR-34 knockout animals. 21 Collectively, these results implicate the miR-34 family in modulating the expression of other miR-NAs via its target TFs.…”

Section: Mirna-seq Reveals Distinctive Mirna Gene Expression Patternsmentioning

confidence: 95%

Identification of miR-34 regulatory networks in settings of disease and antimiR-therapy: Implications for treating cardiac pathology and other diseases

et al. 2016

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Expression of the miR-34 family (miR-34a, -34b, -34c) is elevated in settings of heart disease, and inhibition with antimiR-34a/antimiR-34 has emerged as a promising therapeutic strategy. Under chronic cardiac disease settings, targeting the entire miR-34 family is more effective than targeting miR-34a alone. The identification of transcription factor (TF)-miRNA regulatory networks has added complexity to understanding the therapeutic potential of miRNA-based therapies. Here, we sought to determine whether antimiR-34 targets secondary miRNAs via TFs which could contribute to antimiR-34-mediated protection. Using miRNA-Seq we identified differentially regulated miRNAs in hearts from mice with cardiac pathology due to transverse aortic constriction (TAC), and focused on miRNAs which were also regulated by antimiR-34. Two clusters of stress-responsive miRNAs were classified as "pathological" and "cardioprotective," respectively. Using ChIPBase we identified 45 TF binding sites on the promoters of "pathological" and "cardioprotective" miRNAs, and 5 represented direct targets of miR-34, with the capacity to regulate other miRNAs. Knockdown studies in a cardiomyoblast cell line demonstrated that expression of 2 "pathological" miRNAs (let-7e, miR-31) was regulated by one of the identified TFs. Furthermore, by qPCR we confirmed that expression of let-7e and miR-31 was lower in hearts from antimiR-34 treated TAC mice; this may explain why targeting the entire miR-34 family is more effective than targeting miR-34a alone. Finally, we showed that Acsl4 (a common target of miR-34, let-7e and miR-31) was increased in hearts from TAC antimiR-34 treated mice. In summary, antimiR-34 regulates the expression of other miRNAs and this has implications for drug development.

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Early Targets of miR-34a in Neuroblastoma

Cited by 32 publications

References 75 publications

Targeting long non-coding RNA-TUG1 inhibits tumor growth and angiogenesis in hepatoblastoma

Targeting long non-coding RNA-TUG1 inhibits tumor growth and angiogenesis in hepatoblastoma

LYAR promotes colorectal cancer cell mobility by activating galectin-1 expression

Identification of miR-34 regulatory networks in settings of disease and antimiR-therapy: Implications for treating cardiac pathology and other diseases

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