“Snorkeling” for missing players in cancer

Taulli, Riccardo; Pandolfi, Pier Paolo

doi:10.1172/jci63549

Cited by 16 publications

(10 citation statements)

References 25 publications

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“…miR-206 is regarded as a potentially druggable molecule, abrogating RMS growth in xenotransplant model (27) and inducing a switch toward the differentiated phenotype (49). Again, we observed the same effect in mice treated with HO-1 inhibitor.…”

Section: Discussionsupporting

confidence: 76%

Heme Oxygenase-1 Controls an HDAC4-miR-206 Pathway of Oxidative Stress in Rhabdomyosarcoma

et al. 2016

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Rhabdomyosarcoma (RMS) is an aggressive soft tissue cancer characterized by disturbed myogenic differentiation. Here we report a role for the oxidative stress response factor HO-1 in progression of RMS. We found that HO-1 was elevated and its effector target miR-206 decreased in RMS cell lines and clinical primary tumors of the more aggressive alveolar phenotype (aRMS). In embryonal RMS (eRMS), HO-1 expression was induced by Pax3/7-FoxO1, an aRMS hallmark oncogene, followed by a drop in miR-206 levels. Inhibition of HO-1 by tin protoporphyrin (SnPP) or siRNA downregulated Pax3/7-FoxO1 target genes and induced a myogenic program in RMS.These effects were not mediated by altered myoD expression; instead, cells with elevated HO-1 produced less reactive oxygen species, resulting in nuclear localization of HDAC4 and miR-206 repression. HO-1 inhibition by SnPP reduced growth and vascularization of RMS tumors in vivo accompanied by induction of miR-206. Effects of SnPP on miR-206 expression and RMS tumor growth were mimicked by pharmacologic inhibition of HDAC. Thus, HO-1 inhibition activates an miR-206-dependent myogenic program in RMS, offering a novel therapeutic strategy for treatment of this malignancy.

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Section: Discussionsupporting

confidence: 76%

Heme Oxygenase-1 Controls an HDAC4-miR-206 Pathway of Oxidative Stress in Rhabdomyosarcoma

et al. 2016

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“…In light of their presumptive stable expression, some snoRNAs have been selected as reference genes in studies investigating the expression of microRNAs in human neoplasm (Gee et al., 2011). However, recent findings have challenged these assumptions, revealing that snoRNAs can migrate to the cytoplasm and modulate a wide range of cellular functions (Taulli and Pandolfi, 2012). At the same time, it has become evident that snoRNA expression patterns are deregulated in cancer cells and in serum samples from cancer patients (Baraniskin et al., 2013).…”

Section: Introductionmentioning

confidence: 99%

Integrated analysis of the prostate cancer small‐nucleolar transcriptome reveals SNORA55 as a driver of prostate cancer progression

et al. 2015

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Metastasis is the primary cause of death in prostate cancer (PCa) patients. Small nucleolar RNAs (snoRNAs) have long been considered “housekeeping” genes with no relevance for cancer biology. Emerging evidence has challenged this assumption, suggesting that snoRNA expression is frequently modulated during cancer progression. Despite this, no study has systematically addressed the prognostic and functional significance of snoRNAs in PCa.We performed RNA Sequencing on paired metastatic/non‐metastatic PCa xenografts derived from clinical specimens. The clinical significance of differentially expressed snoRNAs was further investigated in two independent primary PCa cohorts (131 and 43 patients, respectively). The snoRNA demonstrating the strongest association with clinical outcome was quantified in PCa patient‐derived serum samples and its functional relevance was investigated in PCa cells via gene expression profiling, pathway analysis and gene silencing.Our comparison revealed 21 differentially expressed snoRNAs in the metastatic vs. non‐metastatic xenografts. Of those, 12 were represented in clinical databases and were further analyzed. SNORA55 emerged as a predictor of shorter relapse‐free survival (results confirmed in two independent databases). SNORA55 was reproducibly detectable in serum samples from PCa patients. SNORA55 silencing in PCa cell lines significantly inhibited cell proliferation and migration. Pathway analysis revealed that SNORA55 expression is significantly associated with growth factor signaling and pro‐inflammatory cytokine expression in PCa.Our results demonstrate that SNORA55 up‐regulation predicts PCa progression and that silencing this non‐coding gene affects PCa cell proliferation and metastatic potential, thus positioning it as both a novel biomarker and therapeutic target.

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“…In addition, although Drosophila lacks a canonical telomerase, Drosophila dyskerin is essential for fly viability and its depletion causes a large variety of developmental defects . Finally, snoRNPs have recently gained an important role in several pathologies, including cancer .…”

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confidence: 99%

A new role for human dyskerin in vesicular trafficking

et al. 2017

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Dyskerin is an essential, conserved, multifunctional protein found in the nucleolus, whose loss of function causes the rare genetic diseases X‐linked dyskeratosis congenita and Hoyeraal‐Hreidarsson syndrome. To further investigate the wide range of dyskerin's biological roles, we set up stable cell lines able to trigger inducible protein knockdown and allow a detailed analysis of the cascade of events occurring within a short time frame. We report that dyskerin depletion quickly induces cytoskeleton remodeling and significant alterations in endocytic Ras‐related protein Rab‐5A/Rab11 trafficking. These effects arise in different cell lines well before the onset of telomere shortening, which is widely considered the main cause of dyskerin‐related diseases. Given that vesicular trafficking affects many homeostatic and differentiative processes, these findings add novel insights into the molecular mechanisms underlining the pleiotropic manifestation of the dyskerin loss‐of‐function phenotype.

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“Snorkeling” for missing players in cancer

Cited by 16 publications

References 25 publications

Heme Oxygenase-1 Controls an HDAC4-miR-206 Pathway of Oxidative Stress in Rhabdomyosarcoma

Heme Oxygenase-1 Controls an HDAC4-miR-206 Pathway of Oxidative Stress in Rhabdomyosarcoma

Integrated analysis of the prostate cancer small‐nucleolar transcriptome reveals SNORA55 as a driver of prostate cancer progression

A new role for human dyskerin in vesicular trafficking

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