1,721,033 research outputs found
RPSAP52 lncRNA inhibits p21Waf1/CIP expression by interacting with the RNA binding protein HuR
No full textLong-non coding RNAs have been recently demonstrated to have an important role in fundamental biological processes, and their deregulated expression has been found in several human neoplasias. Our group has recently reported a drastic overexpression of the lncRNA RPSAP52 in pituitary adenomas. We have shown that this lncRNA increased cell proliferation by upregulating the expression of the chromatinic proteins HMGA1 and HMGA2, functioning as a ceRNA through competitively binding to miR-15a, miR-15b and miR-16. The aim of this work has been to identify further mechanisms by which RPSAP52 overexpression could contribute to the development of pituitary adenomas. We investigated the involvement of RPSAP52 in the modulation of the expression of cell cycle-related genes, such as p21Waf1/Cip, whose deregulation plays a critical role in pituitary cell transformation. We report that RPSAP52, interacting with the RNA binding protein HuR, favors the delocalization of miR-15a, miR-15b and miR-16on the cyclin45 dependent kinase inhibitor p21Waf1/Cip1 that, accordingly, results downregulated in pituitary adenomas. A RIPseq analysis performed on cells overexpressing RPSAP52 identified 40 mRNAs enriched in AGO2 immunoprecipitated samples. Among them we focused on GAS8 (Growth Arrest-Specific Protein 8) gene. Consistently, GAS8 expression was downregulated in all the analyzed pituitary adenomas with respect to normal pituitary and in RPSAP52-overepressing cells, supporting the role of RPSAP52 in addressing genes involved in growth inhibition and cell cycle arrest to miRNA-induced degradation. This study unveils another RPSAP52-mediated molecular mechanism in pituitary tumorigenesis
Current shreds of evidence on the anticancer role of EGCG in triple negative breast cancer: an update of the current state of knowledge
No full textTriple-Negative Breast Cancer (TNBC), represents a subtype of breast cancer in which the estrogens receptor (ER) negative, the progesterone receptor (PR) negative and the human epidermal growth factor receptor 2 (HER2) negative, are not expressed. Thusly, TNBC does not respond to hormonal therapies or to those targeting the HER2 protein receptors. To overcome this flawed issue, new alternative therapies based on the use of natural substances, as the (-) - epigallocatechin 3-gallate (EGCG), has been proposed. It is largely documented that EGCG, the principal constituent of green tea, has suppressive effects on different types of cancer, including breast cancer, through the regulation of different signaling pathways. Thus, is reasonable to assume that EGCG could be viewed as a therapeutic option for the prevention and the treatment of TNBC. Here, we summarizing these promising results with the scope of turn a light on the potential roles of EGCG in the treatment of TNBC patients
Shining a Light on the Effects of the Combination of (–)-Epigallocatechin-3-gallate and Tapentadol on the Growth of Human Triple-negative Breast Cancer Cells
No full textBackground/aim: Breast cancer is characterized by a high rate of mortality and is considered one of the deadliest types of cancer. It is of note that (-)-epigallocatechin-3-gallate (EGCG), the principal catechin of green tea, is able to hinder the growth of MDA-MB-231 breast cancer cells by influencing different signaling pathways, including apoptosis. Furthermore, EGCG is also used in the treatment of bone cancer pain. Tapentadol, an opioid drug acting at the level of noradrenaline (norepinephrine) reuptake inhibition and μ-opioid receptor, is able to modulate bone cancer pain and influence cancer cell viability by regulating apoptosis. Materials and methods: In vitro assays were performed on triple-negative MDA-MB-231 cells treated with tapentadol (1, 5, 10, 20, 40 and 80 μg/ml) and EGCG (1, 10, 20, 40, 80, 160 μmol/l), alone and in combination. The effects of EGCG and TAP on viability were determined by wound-healing and MTT assays, while cell migration was assessed by transwell migration. Results: Cell proliferation, viability and apoptosis of MDA-MB-231 cells were impaired by the combination of EGCG and tapentadol. Specifically, our data show that EGCG and TAP reduced the proliferation of MDA-MB-231 cells by impairing cell-cycle progression (p<0.05). These findings suggest that the combination of these substances may represent a new strategy for the treatment of patients suffering from triple-negative breast cancer
Critical role of HMGA proteins in cancer cell chemoresistance
No full textThe high-mobility group A (HMGA) proteins are frequently overexpressed in human malignancies and correlate with the presence of metastases and reduced patient survival. Here, we highlight the main studies evidencing a critical role of HMGA in chemoresistance, mainly by activating Akt signaling, impairing p53 activity, and regulating the expression of microRNAs that target genes involved in the susceptibility of cancer cells to antineoplastic agents. Therefore, these studies account for the association of HMGA overexpression with patient poor outcome, indicating the impairment of HMGA as a fascinating perspective for effectively improving cancer therapy
I composti organo-metallici: nuove molecole nella terapia oncologica
No full textLa Chimica inorganica applicata alla Biomedicina,
nota oggi come la medicina elementare, è un importante
campo della Chimica, poco esplorato.
Essa offre il potenziale per la progettazione di nuovi
agenti terapeutici e diagnostici utili al trattamento e alla
comprensione delle patologie oncologiche, che sono ora
intrattabili [1-3].
Gli Elementi inorganici hanno un ruolo cruciale nei processi
biologici e biomedici; infatti, è evidente che molti
composti organici utilizzati in medicina non hanno una
modalità di azione chiara; alcuni di essi sono attivati o
biotrasformati da ioni metallici, tra cui i metallo-enzimi
[4], altri hanno un effetto diretto o indiretto sul metabolismo
degli ioni metallici.
La Biomedicina della chimica inorganica offre reali possibilità
per le industrie farmaceutiche, che tradizionalmente
sono dominate dalla chimica organica, per la scoperta
di farmaci innovativi con nuovi meccanismi d’azione.
Questo campo è stato stimolato dal successo del cisplatino,
il farmaco antitumorale più venduto al mondo, e dai complessi
del platino con ridotta tossicità, mentre l’attività
contro i tumori chemio-resistenti è attualmente in sperimentazione
clinica. Altri complessi organo-metallici, come
il titanocene dicloruro, sono stati somministrati ai pazienti
mostrando una promettente attività antimetastatica.
Recenti progressi nella comprensione della chimica di coordinazione
e biochimica dei metallo-farmaci, come gli
antiartritici e farmaci antiulcera, aprono all’individuazione
di nuovi composti farmacologicamente attivi. La
crescente conoscenza della chimica organo-metallica fornirà
gli elementi per la progettazione di nuovi composti nella terapia del cancro
I composti organo-metallici: nuove molecole nella terapia oncologica
No full textLa Chimica inorganica applicata alla Biomedicina,
nota oggi come la medicina elementare, è un importante
campo della Chimica, poco esplorato.
Essa offre il potenziale per la progettazione di nuovi
agenti terapeutici e diagnostici utili al trattamento e alla
comprensione delle patologie oncologiche, che sono ora
intrattabili [1-3].
Gli Elementi inorganici hanno un ruolo cruciale nei processi
biologici e biomedici; infatti, è evidente che molti
composti organici utilizzati in medicina non hanno una
modalità di azione chiara; alcuni di essi sono attivati o
biotrasformati da ioni metallici, tra cui i metallo-enzimi
[4], altri hanno un effetto diretto o indiretto sul metabolismo
degli ioni metallici.
La Biomedicina della chimica inorganica offre reali possibilità
per le industrie farmaceutiche, che tradizionalmente
sono dominate dalla chimica organica, per la scoperta
di farmaci innovativi con nuovi meccanismi d’azione.
Questo campo è stato stimolato dal successo del cisplatino,
il farmaco antitumorale più venduto al mondo, e dai complessi
del platino con ridotta tossicità, mentre l’attività
contro i tumori chemio-resistenti è attualmente in sperimentazione
clinica. Altri complessi organo-metallici, come
il titanocene dicloruro, sono stati somministrati ai pazienti
mostrando una promettente attività antimetastatica.
Recenti progressi nella comprensione della chimica di coordinazione
e biochimica dei metallo-farmaci, come gli
antiartritici e farmaci antiulcera, aprono all’individuazione
di nuovi composti farmacologicamente attivi. La
crescente conoscenza della chimica organo-metallica fornirà
gli elementi per la progettazione di nuovi composti nella terapia del cancro
Characterization of HMGA1P6 transgenic mouse embryonic fibroblasts
No full text: Latest studies have shown that deregulated pseudogene transcripts contribute to cancer working as competing endogenous RNAs. Our research group has recently demonstrated that the overexpression of two HMGA1 pseudogenes, HMGA1P6 and HMGA1P7, has a critical role in cancer progression. These pseudogenes work sustaining the expression of HMGA1 and other cancer-related genes. We generated a mouse model overexpressing HMGA1P6 to better study the HMGA1-pseudogene function in a more physiological context. Here, we show the proliferation rate and the susceptibility to senescence of mouse embryonic fibroblasts obtained from HMGA1P6-overexpressing mice to better characterize the HMGA1-pseudogene function. Indeed, our study reports that mouse embryonic fibroblasts (MEFs) derived from HMGA1P6 mice express higher HMGA1 mRNA and protein levels. Moreover, these cells grow faster and senesce later than wild-type sustaining the oncogenic role of ceRNA crosstalk mediated by HMGA1Ps
HMGA1-pseudogenes and cancer
No full textPseudogenes are DNA sequences with high homology to the corresponding functional gene, but, because of the accumulation of various mutations, they have lost their initial functions to code for proteins. Consequently, pseudogenes have been considered until few years ago dysfunctional relatives of the corresponding ancestral genes, and then useless in the course of genome evolution. However, several studies have recently established that pseudogenes are owners of key biological functions. Indeed, some pseudogenes control the expression of functional genes by competitively binding to the miRNAs, some of them generate small interference RNAs to negatively modulate the expression of functional genes, and some of them even encode functional mutated proteins. Here, we concentrate our attention on the pseudogenes of the HMGA1 gene, that codes for the HMGA1a and HMGA1b proteins having a critical role in development and cancer progression. In this review, we analyze the family of HMGA1 pseudogenes through three aspects: classification, characterization, and their possible function and involvement in cancer
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