miR-15a and 16-1 Are Downregulated in CD4(+) T Cells of Multiple Sclerosis Relapsing Patients

The pathology of relapsing-remitting multiple sclerosis (RR-MS) is largely attributed to activated autoreactive effector T lymphocytes. The influence of microRNAs on the immune response has been shown to occur in different pathways of lymphocyte differentiation and function. Here, the expression of the miRNAs miR-15a/161 in PBMC, CD4(+), and CD8(+) from RR-MS patients has been investigated. BCL2, a known miR-15a/16-1 target, has also been analyzed. The results have shown that miR-15a/16-1 is downregulated in CD4(+) T cells, whereas BCL2 is highly expressed in RR-MS patients only. Our data suggest that miR-15a/16-1 can also modulate the BCL2 gene expression in CD4(+) T cells from RR-MS patients, thereby affecting apoptosis processes.

Increased expression of miR-221 is associated with shorter overall survival in T-cell acute lymphoid leukemia

Background: CD56 expression has been associated with a poor prognosis in lymphoid neoplasms, including T-cell acute lymphoblastic leukemia (T-ALL). MicroRNAs (miRNAs) play an important role in lymphoid differentiation, and aberrant miRNA expression has been associated with treatment outcome in lymphoid malignancies. Here, we evaluated miRNA expression profiles in normal thymocytes, mature T-cells, and T-ALL samples with and without CD56 expression and correlated microRNA expression with treatment outcome. Methods: The gene expression profile of 164 miRNAs were compared for T-ALL/CD56+ (n=12) and T-ALL/CD56- (n=36) patients by Real-Time Quantitative PCR. Based on this analysis, we decided to evaluate miR-221 and miR-374 expression in individual leukemic and normal samples. Results: miR-221 and miR-374 were expressed at significantly higher levels in T-ALL/CD56+ than in T-ALL/CD56- cells and in leukemic blasts compared with normal thymocytes and peripheral blood (PB) T-cells. Age at diagnosis (15 or less vs grater than 15 years; HR: 2.19, 95% CI: 0.98-4.85; P=0.05), miR-221 expression level (median value as cut off in leukemic samples; HR: 3.17, 95% CI: 1.45-6.92; P=0.004), and the expression of CD56 (CD56- vs CD56+; HR: 2.99, 95% CI: 1.37-6.51; P=0.006) were predictive factors for shorter overall survival; whereas, only CD56 expression (HR: 2.73, 95% CI: 1.03-7.18; P=0.041) was associated with a shorter disease-free survival rate. Conclusions: miR-221 is highly expressed in T-ALL and its expression level may be associated with a poorer prognosis.

Caratterizzazione del soppressore tumorale miR-101 nel colon carcinoma

I microRNA sono una classe di piccole molecole di RNA non codificante che controllano la stabilità di numerosi RNA messaggeri, perciò sono considerati come “master regulator” dell’espressione genica. Ogni tumore è caratterizzato da un profilo di espressione alterato dei microRNA. Il miR-101 è un oncosoppressore represso nei tessuti tumorali ed è candidato come biomarcatore del cancro colon-rettale. È regolato da numerosi eventi fisiologici e patologici, come angiogenesi e carcinogenesi. Gli eventi molecolari coinvolti nella regolazione dell’espressione del miR-101 sono scarsamente conosciuti, poiché è trascritto da due loci genici non caratterizzati. L’obiettivo di questo lavoro è di caratterizzare i geni del miR-101 ed individuarne i regolatori molecolari coinvolti nella cancerogenesi colon-rettale.

Antisemiten sind mir egal – Juden aber nicht. (Gli antisemiti non mi interessano, gli ebrei invece sì). Proposta di traduzione del saggio „ Antisemiten sind mir egal „ di Maxim Biller

Questo elaborato si basa sulla proposta di traduzione del saggio letterario giornalistico "Antisemiten sind mir egal" di Maxim Biller pubblicato sulla Zeit (Nº 41/2014) il 18.10.2014. L'idea di usare questo testo è nata da una lezione di letteratura tedesca svolta quest'anno durante il secondo semestre dal professor Giovanni Nadiani. Sicuramente questa traduzione è stata fin dall'inizio una grande sfida vista la difficoltà del testo dovuta al tema legato all'attualitá e ricco di riferimenti alla cultura tedesca e israeliana, per i quali si è rivelato necessario l'uso delle note a piè di pagina con l’obiettivo di agevolare la comprensione al lettore italiano. Una volta superate le difficoltà iniziali, sviluppare questo elaborato si è rivelato molto interessante e mi ha arricchita molto sia a livello personale sia a livello formativo. Per poter rendere il testo tradotto in modo adeguato, il traduttore deve prima comprendere il messaggio originario. La comprensione del linguaggio è possibile solo se emittente e destinatario condividono il contesto situazionale e la cultura di riferimento. Per riuscire a comprendere totalmente il messaggio, i destinatari del testo tradotto potrebbero avere difficoltà interpretative. Da qui l’esigenza di aggiungere parti esplicative per colmare e sanare le divergenze tra cultura di partenza e di arrivo. Questo lavoro è stato lungo e impegnativo ma anche fonte di grande soddisfazione e uno stimolo ad approfondire non solo la mia conoscenza della lingua tedesca, ma anche quella della mia lingua madre. Infine spero con la mia proposta di traduzione di essere riuscita ad avvicinare il pubblico italiano a questo saggio, che mette in discussione una tematica di grande attualità e su cui è sempre bene riflettere.

miR-34a and miR-15a/16 are co-regulated in non-small cell lung cancer and control cell cycle progression in a synergistic and Rb-dependent manner

microRNAs (miRNAs) are small non-coding RNAs that are frequently involved in carcinogenesis. Although many miRNAs form part of integrated networks, little information is available how they interact with each other to control cellular processes. miR-34a and miR-15a/16 are functionally related; they share common targets and control similar processes including G1-S cell cycle progression and apoptosis. The aim of this study was to investigate the combined action of miR-34a and miR-15a/16 in non-small cell lung cancer (NSCLC) cells.

miR-21 functionally interacts with the 3'UTR of chemokine CCL20 and down-regulates CCL20 expression in miR-21 transfected colorectal cancer cells

As deregulation of miRNAs and chemokine CCL20 was shown to play a role in colorectal cancer (CRC) pathogenesis, we analyzed the functional interactions of candidate miRNAs with CCL20 mRNA. After target prediction software programs indicated a role for miR-21 in CCL20 regulation, we applied the luciferase reporter assay system to demonstrate that miR-21 functionally interacts with the 3'UTR of CCL20 mRNA and down-regulates CCL20 in miR-21 mimic transfected CRC cell lines (Caco-2, SW480 and SW620). Thus, regulation of CCL20 expression by miR-21 might be a regulatory mechanism involved in progression of CRC.

Inhibition of the miR-143/145 cluster attenuated neutrophil differentiation of APL cells

MicroRNAs can influence hematopoietic cell lineage commitment and aberrant expression of hematopoietic miRNAs contributes to AML pathology. We found that miR-143 and miR-145 expression is significantly repressed in primary AML patient samples as compared to neutrophils of healthy donors. Further analysis revealed impaired neutrophil differentiation of APL cells upon inhibition of miR-145 expression. Lastly, we identified p73 as transcriptional regulator of miR-143/145 during neutrophil differentiation of APL cells. Our data suggest that low miR-145 levels in APL, possibly due to aberrant expression of p73 transcription factors, contribute to the differentiation block seen in this disease.

miR-199a-5p regulates urothelial permeability and may play a role in bladder pain syndrome

Defects in urothelial integrity resulting in leakage and activation of underlying sensory nerves are potential causative factors of bladder pain syndrome, a clinical syndrome of pelvic pain and urinary urgency/frequency in the absence of a specific cause. Herein, we identified the microRNA miR-199a-5p as an important regulator of intercellular junctions. On overexpression in urothelial cells, it impairs correct tight junction formation and leads to increased permeability. miR-199a-5p directly targets mRNAs encoding LIN7C, ARHGAP12, PALS1, RND1, and PVRL1 and attenuates their expression levels to a similar extent. Using laser microdissection, we showed that miR-199a-5p is predominantly expressed in bladder smooth muscle but that it is also detected in mature bladder urothelium and primary urothelial cultures. In the urothelium, its expression can be up-regulated after activation of cAMP signaling pathways. While validating miR-199a-5p targets, we delineated novel functions of LIN7C and ARHGAP12 in urothelial integrity and confirmed the essential role of PALS1 in establishing and maintaining urothelial polarity and junction assembly. The present results point to a possible link between miR-199a-5p expression and the control of urothelial permeability in bladder pain syndrome. Up-regulation of miR-199a-5p and concomitant down-regulation of its multiple targets might be detrimental to the establishment of a tight urothelial barrier, leading to chronic pain.