miR-21: an oncomir on strike in prostate cancer

<p>Abstract</p> <p>Background</p> <p>Aberrant expression of microRNAs, small non-coding RNA molecules that post-transcriptionally repress gene expression, seems to be causatively linked to the pathogenesis of cancer. In this context, miR-21 was found to be overexpressed in different human cancers (e.g. glioblastoma, breast cancer). In addition, it is thought to be endowed with oncogenic properties due to its ability to negatively modulate the expression of tumor-suppressor genes (e.g. <it>PTEN</it>) and to cause the reversion of malignant phenotype when knocked- down in several tumor models. On the basis of these findings, miR-21 has been proposed as a widely exploitable cancer-related target. However, scanty information is available concerning the relevance of miR-21 for prostate cancer. In the present study, we investigated the role of miR-21 and its potential as a therapeutic target in two prostate cancer cell lines, characterized by different miR-21 expression levels and <it>PTEN </it>gene status.</p> <p>Results</p> <p>We provide evidence that miR-21 knockdown in prostate cancer cells is not sufficient <it>per se </it>i) to affect the proliferative and invasive potential or the chemo- and radiosensitivity profiles or ii) to modulate the expression of the tumor-suppressors PTEN and Pdcd4, which in other tumor types were found to be regulated by miR-21. We also show that miR-21 is not differently expressed in carcinomas and matched normal tissues obtained from 36 untreated prostate cancer patients subjected to radical prostatectomy.</p> <p>Conclusions</p> <p>Overall, our data suggest that miR-21 is not a central player in the onset of prostate cancer and that its single hitting is not a valuable therapeutic strategy in the disease. This supports the notion that the oncogenic properties of miR-21 could be cell and tissue dependent and that the potential role of a given miRNA as a therapeutic target should be contextualized with respect to the disease.</p

Stranieri. Itinerari di vita studentesca tra XIII e XVIII secolo.

Questo volume osserva l’università come punto di incontro tra uomini di età diverse e di origini geografiche molteplici. Ciò vale in particolare modo per l’Ateneo patavino, che deve le sue origini proprio a una migrazione di scolari. Un evento circoscritto, che tuttavia rientra nel fenomeno più ampio e diffuso della mobilità accademica che caratterizza il medioevo e la prima età moderna. Nel corso del medioevo – con un’accelerazione notevole a partire dal XII secolo – maestri e scolari furono indotti a muoversi verso i centri del sapere – monasteri, scuole, cattedrali, conventi, università – alla ricerca degli ambienti più stimolanti dal punto di vista intellettuale e delle condizioni che meglio garantissero l’apprendimento, quali ad esempio la presenza di ricche biblioteche o le lezioni dei docenti più illustri. I cosiddetti clerici vagantes costituivano un gruppo estremamente eterogeneo dal punto di vista geografico e sociale, provenendo da tutto il continente europeo. Una mobilità che ha continuato a marcare la vita accademica, in particolare di Padova, la cui comunità studentesca si è da sempre arricchita di un’ampia componente proveniente dall’esterno della città: dall’impero tedesco alla Francia, dalla Polonia alla Grecia, ma anche dall’Italia meridionale. I dati utilizzati nel volume provengono da un database che raccoglie più di 70 000 laureati a Padova, costruito per l’ottocentenario dell’Università e realizzato anche grazie al lavoro di molti studenti, che vi hanno dedicato il loro impegno e le loro energie

A positive feedback loop between ESE1/ELF3 and NF-κB promotes prostate cancer progression

ETS transcription factors regulate important signaling pathways involved in cell differentiation and development in many tissues and recently have emerged as important players in prostate cancer. Inflammation has shown to be important for the initiation and the progression of prostate cancer. However, the mechanism has not been elucidated. Here, we report a novel mechanism leading to oncogenic activation of the ETS factor ESE1/ELF3 in prostate tumors. Through microarray and immunohystochemical analysis we found that ESE1/ELF3 is overexpressed in human primary and metastatic tumors. Moreover, it mediates transforming phenotypes in vitro and in vivo and induced an inflammatory transcriptome with changes in relevant oncogenic pathways. ESE1/ELF3 was induced by IL-1β through NF-κB, and was a crucial mediator of the phenotypic and transcriptional changes induced by IL-1β in prostate cancer cells. Here we report that ESE1/ELF3 interacted with the NF-κB subunits p65 and p50, enhanced their nuclear translocation and transcriptional activity and induced p50 transcription. Supporting these findings, gene expression profiling revealed an enrichment of NF-κB effector functions in prostate cancer cells or tumors expressing high levels of ESE1/ELF3. Furthermore, we observed concordant upregulation of ESE1/ELF3 and NF-κB activation in human prostate tumors that was associated with adverse prognosis in multiple cohorts of primary prostate tumors analyzed. Collectively, our results define an important new mechanistic link between inflammatory signaling and the progression of prostate cancer. Furthermore these studies indicate the possibility to apply context-dependent therapeutic strategies to a subgroup of tumors characterized by ESE1/ELF3 and NF-κB activation and with aggressive clinical features

ETS Transcription Factor ESE1/ELF3 Orchestrates a Positive Feedback Loop That Constitutively Activates NF- B and Drives Prostate Cancer Progression

Chromosomal translocations leading to deregulated expression of ETS transcription factors are frequent in prostate tumors. Here, we report a novel mechanism leading to oncogenic activation of the ETS factor ESE1/ELF3 in prostate tumors. ESE1/ELF3 was overexpressed in human primary and metastatic tumors. It mediated transforming phenotypes in vitro and in vivo and induced an inflammatory transcriptome with changes in relevant oncogenic pathways. ESE1/ELF3 was induced by interleukin (IL)-1\u3b2 through NF-kB and was a crucial mediator of the phenotypic and transcriptional changes induced by IL-1\u3b2 in prostate cancer cells. This linkage was mediated by interaction of ESE1/ELF3 with the NF-\u3baB subunits p65 and p50, acting by enhancing their nuclear translocation and transcriptional activity and by inducing p50 transcription. Supporting these findings, gene expression profiling revealed an enrichment of NF-kB effector functions in prostate cancer cells or tumors expressing high levels of ESE1/ELF3. We observed concordant upregulation of ESE1/ELF3 and NF-\u3baB in human prostate tumors that was associated with adverse prognosis. Collectively, our results define an important new mechanistic link between inflammatory signaling and the progression of prostate cancer

Stranieri. Itinerari di vita studentesca tra XIII e XVIII secolo.

Il volume esamina gli studenti stranieri presso l'Università di Padova nella lunga diacronia, a partire dal XIII fino al XVIII secolo. La mobilità studentesca è analizzata attraverso tre momenti: l'arrivo a Padova; l'inserimento nella città e i diversi aspetti della vita studentesca; il ritorno in patria, i ricordi e le opportunità offerte dal soggiorno patavino