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Inhibiting cancer metabolism by aromatic carbohydrate amphiphiles that act as a...

Brito, Alexandra; Pereira, Patrícia M.; Costa, Diana Soares da; Reis, R. L.; Ulijn, Rein V.; Lewis, Rein V.; Pires, R. A.; Pashkuleva, I.

We report on aromatic N-glucosides that inhibit selectively the cancer metabolism via two coexistent mechanisms: by initial deprivation of the glucose uptake through competitive binding in the glucose binding pocket of GLUT1 and by formation of a sequestering nanoscale supramolecular network at the cell surface through localized (biocatalytic) self-assembly. We demonstrate that the expression of the cancer asso...


Codon misreading tRNAs promote tumor growth in mice

Santos, Mafalda; Pereira, Patrícia M.; Varanda, A. Sofia; Carvalho, Joana; Azevedo, Mafalda; Mateus, Denisa D.; Mendes, Nuno; Oliveira, Patrícia

Deregulation of tRNAs, aminoacyl-tRNA synthetases and tRNA modifying enzymes are common in cancer, raising the hypothesis that protein synthesis efficiency and accuracy (mistranslation) are compromised in tumors. We show here that human colon tumors and xenograft tumors produced in mice by two epithelial cancer cell lines mistranslate 2- to 4-fold more frequently than normal tissue. To clarify if protein mistra...


Differences in the expression pattern of HCN isoforms among mammalian tissues: ...

Calejo, Ana I.; Reverendo, Marisa; Silva, Virgília S.; Pereira, Patrícia M.; Santos, Manuel A. S.; Zorec, Robert; Gonçalves, Paula P.

Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels play a critical role in a broad range of cell types, but the expression of the various HCN isoforms is still poorly understood. In the present study we have compared the expression of HCN isoforms in rat excitable and non-excitable tissues at both the mRNA and protein levels. Real-time PCR and Western blot analysis revealed distinct expression p...


TRNA mutations that affect decoding fidelity deregulate development and the pro...

Reverendo, Marisa; Soares, Ana R.; Pereira, Patrícia M.; Carreto, Laura; Ferreira, Violeta; Gatti, Evelina; Pierre, Philippe; Moura, Gabriela R.

Mutations in genes that encode tRNAs, aminoacyl-tRNA syntheases, tRNA modifying enzymes and other tRNA interacting partners are associated with neuropathies, cancer, type-II diabetes and hearing loss, but how these mutations cause disease is unclear. We have hypothesized that levels of tRNA decoding error (mistranslation) that do not fully impair embryonic development can accelerate cell degeneration through pr...


Differential gene expression analysis in Enchytraeus albidus exposed to natural...

Novais, Sara C.; Howcroft, Clara F.; Carreto, Laura; Pereira, Patrícia M.; Santos, Manuel A. S.; De Coen, Wim; Soares, Amadeu M. V. M.

The soil oligochaete Enchytraeus albidus is a standard test organism used in biological testing for Environmental Risk Assessment (ERA). Although effects are known at acute and chronic level through survival, reproduction and avoidance behaviour endpoints, very little is known at the sub-cellular and molecular levels. In this study, the effects of soil properties (clay, organic matter and pH) and of the chemica...


Dre-miR-2188 targets Nrp2a and mediates proper intersegmental vessel developmen...

Soares, Ana R.; Reverendo, Marisa; Pereira, Patrícia M.; Nivelles, Olivier; Pendeville, Hélène; Bezerra, Ana Rita; Moura, Gabriela R.; Struman, Ingrid

Background - MicroRNAs (miRNAs) are a class of small RNAs that are implicated in the control of eukaryotic gene expression by binding to the 3′UTR of target mRNAs. Several algorithms have been developed for miRNA target prediction however, experimental validation is still essential for the correct identification of miRNA targets. We have recently predicted that Neuropilin2a (Nrp2a), a vascular endothelial growt...


Ethanol exposure induces upregulation of specific microRNAs in zebrafish embryos

Soares, Ana Raquel; Pereira, Patrícia M.; Ferreira, Violeta; Reverendo, Marisa; Simões, João; Bezerra, Ana Rita; Moura, Gabriela R.

Prenatal exposure to ethanol leads to a myriad of developmental disorders known as fetal alcohol spectrum disorder, often characterized by growth and mental retardation, central nervous system damage, and specific craniofacial dysmorphic features. The mechanisms of ethanol toxicity are not fully understood, but exposure during development affects the expression of several genes involved in cell cycle control, a...


Lack of microRNA-101 causes E-cadherin functional deregulation through EZH2 up-...

Carvalho, Joana; van Grieken, Nicole C.; Pereira, Patrícia M.; Sousa, Sónia; Tijssen, Marianne; Buffart, Tineke E.; Diosdado, Begoña; Grabsch, Heike

E-cadherin expression disruption is commonly observed in metastatic epithelial cancers and is a crucial step in gastric cancer (GC) initiation and progression. As aberrant expression of microRNAs often perturb the normal expression/function of pivotal cancer-related genes, we characterized and dissected a pathway that causes E-cadherin dysfunction via loss of microRNA-101 and up-regulation of EZH2 expression in...


MicroRNA expression variability in human cervical tissues

Pereira, Patrícia M.; Marques, João Paulo; Soares, Ana R.; Carreto, Laura; Santos, Manuel A. S.

MicroRNAs (miRNAs) are short (approximately 22 nt) non-coding regulatory RNAs that control gene expression at the post-transcriptional level. Deregulation of miRNA expression has been discovered in a wide variety of tumours and it is now clear that they contribute to cancer development and progression. Cervical cancer is one of the most common cancers in women worldwide and there is a strong need for a non-inva...


Parallel DNA pyrosequencing unveils new zebrafish microRNAs

Soares, Ana R.; Pereira, Patrícia M.; Santos, Bruno; Egas, Conceição; Gomes, Ana C.; Arrais, Joel; Oliveira, José L.; Moura, Gabriela R.

Background - MicroRNAs (miRNAs) are a new class of small RNAs of approximately 22 nucleotides in length that control eukaryotic gene expression by fine tuning mRNA translation. They regulate a wide variety of biological processes, namely developmental timing, cell differentiation, cell proliferation, immune response and infection. For this reason, their identification is essential to understand eukaryotic biolo...


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