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MiR-182-3p targets TRF2 and impairs tumor growth of triple-negative breast cancer

Dinami, Roberto; Pompili, Luca; Petti, Eleonora; Porru, Manuela; D'Angelo, Carmen; Di Vito, Serena; Rizzo, Angela; Campani, Virginia; De Rosa, Giuseppe

The telomeric repeat-binding factor 2 (TRF2) is a telomere-capping protein that plays a key role in the maintenance of telomere structure and function. It is highly expressed in different cancer types, and it contributes to cancer progression. To date, anti-cancer strategies to target TRF2 remain a challenge. Here, we developed a miRNA-based approach to reduce TRF2 expression. By performing a high-throughput lu...


Microscopy-based phenotypic profiling of infection by Staphylococcus aureus cli...

Lopes, Ines Rodrigues; Alcantara, Laura Maria; Silva, Ricardo Jorge; Josse, Jerome; Vega, Elena Pedrero; Cabrerizo, Ana Marina; Bonhomme, Melanie

Staphylococcus aureus is increasingly recognized as a facultative intracellular pathogen, although the significance and pervasiveness of its intracellular lifestyle remain controversial. Here, we applied fluorescence microscopy-based infection assays and automated image analysis to profile the interaction of 191 S. aureus isolates from patients with bone/joint infections, bacteremia, and infective endocarditis,...


Reprogramming of microRNA expression via E2F1 downregulation promotes Salmonell...

Aguilar, Carmen; Costa, Susana; Maudet, Claire; Vivek-Ananth, R P; Zaldívar-López, Sara; Garrido, Juan J; Samal, Areejit; Mano, Miguel; Eulálio, Ana

Cells infected with pathogens can contribute to clearing infections by releasing signals that instruct neighbouring cells to mount a pro-inflammatory cytokine response, or by other mechanisms that reduce bystander cells' susceptibility to infection. Here, we show the opposite effect: epithelial cells infected with Salmonella Typhimurium secrete host factors that facilitate the infection of bystander cells. We f...


Co-Exposure of Cardiomyocytes to IFN-γ and TNF-α Induces Mitochondrial Dysfunct...

Nunes, João Paulo Silva; Andrieux, Pauline; Brochet, Pauline; Almeida, Rafael Ribeiro; Kitano, Eduardo; Honda, André Kenji; Iwai, Leo Kei

Infection by the protozoan Trypanosoma cruzi causes Chagas disease cardiomyopathy (CCC) and can lead to arrhythmia, heart failure and death. Chagas disease affects 8 million people worldwide, and chronic production of the cytokines IFN-γ and TNF-α by T cells together with mitochondrial dysfunction are important players for the poor prognosis of the disease. Mitochondria occupy 40% of the cardiomyocytes volume a...


Identification of novel therapeutic targets to modulate proteostasis in humans

Pereira, Marisa; Soares, Ana; Mano, Miguel

The average life expectancy of the world's population is increasing, as well as the incidence of age-related diseases (ARD), including cancer, neurodegenerative, and metabolic diseases. One of the most important features, transversal to aging and ARD, is the impairment of the proteome homeostasis network (proteostasis). This is often characterized by an abnormal accumulation of protein aggregates within cells, ...


Che-1/AATF binds to RNA polymerase I machinery and sustains ribosomal RNA gene ...

Sorino, Cristina; Catena, Valeria; Bruno, Tiziana; De Nicola, Francesca; Scalera, Stefano; Bossi, Gianluca; Fabretti, Francesca; Mano, Miguel

Originally identified as an RNA polymerase II interactor, Che-1/AATF (Che-1) has now been recognized as a multifunctional protein involved in cell-cycle regulation and cancer progression, as well as apoptosis inhibition and response to stress. This protein displays a peculiar nucleolar localization and it has recently been implicated in pre-rRNA processing and ribosome biogenesis. Here, we report the identifica...


Sterol regulatory element binding protein 1 couples mechanical cues and lipid m...

Bertolio, Rebecca; Napoletano, Francesco; Mano, Miguel; Maurer-Stroh, Sebastian; Fantuz, Marco; Zannini, Alessandro; Bicciato, Silvio

Sterol regulatory element binding proteins (SREBPs) are a family of transcription factors that regulate lipid biosynthesis and adipogenesis by controlling the expression of several enzymes required for cholesterol, fatty acid, triacylglycerol and phospholipid synthesis. In vertebrates, SREBP activation is mainly controlled by a complex and well-characterized feedback mechanism mediated by cholesterol, a crucial...


Cellular TRIM33 restrains HIV-1 infection by targeting viral integrase for prot...

Ali, Hashim; Mano, Miguel; Braga, Luca; Naseem, Asma; Marini, Bruna; Vu, Diem My; Collesi, Chiara; Meroni, Germana; Lusic, Marina; Giacca, Mauro

Productive HIV-1 replication requires viral integrase (IN), which catalyzes integration of the viral genome into the host cell DNA. IN, however, is short lived and is rapidly degraded by the host ubiquitin-proteasome system. To identify the cellular factors responsible for HIV-1 IN degradation, we performed a targeted RNAi screen using a library of siRNAs against all components of the ubiquitin-conjugation mach...


High-content screen in human pluripotent cells identifies miRNA-regulated pathw...

de Souza Lima, Ildercílio Mota; Schiavinato, Josiane Lilian Dos Santos; Paulino Leite, Sarah Blima; Sastre, Danuta

Background: By post-transcriptionally regulating multiple target transcripts, microRNAs (miRNAs or miR) play important biological functions. H1 embryonic stem cells (hESCs) and NTera-2 embryonal carcinoma cells (ECCs) are two of the most widely used human pluripotent model cell lines, sharing several characteristics, including the expression of miRNAs associated to the pluripotent state or with differentiation....


MiR-16 regulates the pro-tumorigenic potential of lung fibroblasts through the ...

Andriani, Francesca; Majorini, Maria Teresa; Mano, Miguel; Landoni, Elena; Miceli, Rosalba; Facchinetti, Federica; Mensah, Mavis; Fontanella, Enrico

Background: Fibroblasts are crucial mediators of tumor-stroma cross-talk through synthesis and remodeling of the extracellular matrix and production of multiple soluble factors. Nonetheless, little is still known about specific determinants of fibroblast pro-tumorigenic activity in lung cancer. Here, we aimed at understanding the role of miRNAs, which are often altered in stromal cells, in reprogramming fibrobl...


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