MiR-34c may protect lung cancer cells from paclitaxel-induced apoptosis

Catuogno, Silvia (2011) MiR-34c may protect lung cancer cells from paclitaxel-induced apoptosis. [Tesi di dottorato] (Inedito)

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Abstract

MicroRNAs (miRNAs) constitute a class of small non-coding RNAs that negatively regulate gene expression at post-transcriptional level in a sequence specific manner. They are involved in many biological processes, including cell proliferation, apoptosis and differentiation, and are considered as promising new therapeutic targets for cancer. However, the identity of miRNAs involved in apoptosis and their respective targets remain largely unknown. Given the elevated complexity of miRNA regulation of gene expression, we performed a functional screening as an alternative strategy to identify those miRNAs that in lung cancer cells may interfere with the apoptotic process. To this aim we generated a derivative of the non-small cell lung carcinoma A549 cell line in which caspase-8, a critical upstream initiator of apoptosis, can be activated by the administration of the small dimerizer drug AP20187. We found a number of miRNAs that may rescue cell viability from caspase-8 activation. They included miRNAs already described as oncogenic such as miR-17, miR-135, miR-520, but also some miRNAs such as miR-124-1 and miR-34c for which a tumor suppressive role has been instead described or expected. Among them, miR-34c-5p markedly increased resistance to paclitaxel induced apoptosis. We demonstrate that Bmf (Bcl-2 modifying factor) is a target of miR-34c-5p and that its silencing, together with that of c-myc, a known target of miR-34c-5p, contributes to resistance to apoptosis induced by paclitaxel via p53 downregulation.

Tipologia di documento:Tesi di dottorato
Parole chiave:microRNA, apoptosis, NSCLC, p53, c-myc
Settori scientifico-disciplinari MIUR:Area 05 Scienze biologiche > BIO/18 GENETICA
Coordinatori della Scuola di dottorato:
Coordinatore del Corso di dottoratoe-mail (se nota)
Nitsch, Luciolucio.nitsch@unina.it
Tutor della Scuola di dottorato:
Tutor del Corso di dottoratoe-mail (se nota)
de Franciscis, Vittoriodefranci@unina.it
Stato del full text:Inedito
Data:30 Novembre 2011
Numero di pagine:142
Istituzione:Università di Napoli Federico II
Dipartimento o Struttura:Biologia e patologia cellullare e molecolare "L. Califano"
Stato dell'Eprint:Inedito
Scuola di dottorato:Medicina molecolare
Denominazione del dottorato:Genetica e medicina molecolare
Ciclo di dottorato:24
Numero di sistema:8857
Depositato il:09 Dicembre 2011 13:38
Ultima modifica:29 Maggio 2012 12:54

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