Recent findings have identified competing endogenous RNAs (ceRNAs) as the drivers in many disease conditions, including cancers. The ceRNAs indirectly regulate each other by reducing the amount of microRNAs (miRNAs) available to target messenger RNAs (mRNAs). The ceRNA interactions mediated by miRNAs are modulated by a titration mechanism, i.e. large changes in the ceRNA expression levels either overcome, or relieve, the miRNA repression on competing RNAs; similarly, a very large miRNA overexpression may abolish competition. The ceRNAs are also called miRNA decoys or miRNA sponges and encompass different RNAs competing with each other to attract miRNAs for interactions: mRNA, long non-coding RNAs (lncRNAs), pseudogenes, or circular RNAs. Recently, we developed a computational method for identifying ceRNA-ceRNA interactions in breast invasive carcinoma. We were interested in unveiling which lncRNAs could exert the ceRNA activity. We found a drastic rewiring in the cross-talks between ceRNAs from the physiological to the pathological condition. The main actor of this dysregulated lncRNA-associated ceRNA network was the lncRNA PVT1, which revealed a net biding preference towards the miR-200 family members in normal breast tissues. Despite its up-regulation in breast cancer tissues, mimicked by the miR-200 family members, PVT1 stops working as ceRNA in the cancerous state. The specific conditions required for a ceRNA landscape to occur are still far from being determined. Here, we emphasized the importance of the relative concentration of the ceRNAs, and their related miRNAs. In particular, we focused on the withdrawal in breast cancer tissues of the PVT1 ceRNA activity and performed a gene expression and sequence analysis of its multiple isoforms. We found that the PVT1 isoform harbouring the binding site for a representative miRNA of the miR-200 family shows a drastic decrease in its relative concentration with respect to the miRNA abundance in breast cancer tissues, providing a plausibility argument to the breakdown of the sponge program orchestrated by the oncogene PVT1.

Role of the long non-coding RNA PVT1 in the dysregulation of the ceRNA-ceRNA network in human breast cancer / F. Conte, G. Fiscon, M. Chiara, T. Colombo, L. Farina, P. Paci. - In: PLOS ONE. - ISSN 1932-6203. - 12:2(2017 Jan), p. e0171661.e0171661.

Role of the long non-coding RNA PVT1 in the dysregulation of the ceRNA-ceRNA network in human breast cancer

M. Chiara;
2017

Abstract

Recent findings have identified competing endogenous RNAs (ceRNAs) as the drivers in many disease conditions, including cancers. The ceRNAs indirectly regulate each other by reducing the amount of microRNAs (miRNAs) available to target messenger RNAs (mRNAs). The ceRNA interactions mediated by miRNAs are modulated by a titration mechanism, i.e. large changes in the ceRNA expression levels either overcome, or relieve, the miRNA repression on competing RNAs; similarly, a very large miRNA overexpression may abolish competition. The ceRNAs are also called miRNA decoys or miRNA sponges and encompass different RNAs competing with each other to attract miRNAs for interactions: mRNA, long non-coding RNAs (lncRNAs), pseudogenes, or circular RNAs. Recently, we developed a computational method for identifying ceRNA-ceRNA interactions in breast invasive carcinoma. We were interested in unveiling which lncRNAs could exert the ceRNA activity. We found a drastic rewiring in the cross-talks between ceRNAs from the physiological to the pathological condition. The main actor of this dysregulated lncRNA-associated ceRNA network was the lncRNA PVT1, which revealed a net biding preference towards the miR-200 family members in normal breast tissues. Despite its up-regulation in breast cancer tissues, mimicked by the miR-200 family members, PVT1 stops working as ceRNA in the cancerous state. The specific conditions required for a ceRNA landscape to occur are still far from being determined. Here, we emphasized the importance of the relative concentration of the ceRNAs, and their related miRNAs. In particular, we focused on the withdrawal in breast cancer tissues of the PVT1 ceRNA activity and performed a gene expression and sequence analysis of its multiple isoforms. We found that the PVT1 isoform harbouring the binding site for a representative miRNA of the miR-200 family shows a drastic decrease in its relative concentration with respect to the miRNA abundance in breast cancer tissues, providing a plausibility argument to the breakdown of the sponge program orchestrated by the oncogene PVT1.
No
English
Medicine (all); Biochemistry, Genetics and Molecular Biology (all); Agricultural and Biological Sciences (all)
Settore BIO/11 - Biologia Molecolare
Articolo
Esperti anonimi
Ricerca di base
Pubblicazione scientifica
gen-2017
Public Library of Science
12
2
e0171661
e0171661
Pubblicato
Periodico con rilevanza internazionale
http://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0171661&type=printable
scopus
crossref
Aderisco
info:eu-repo/semantics/article
Role of the long non-coding RNA PVT1 in the dysregulation of the ceRNA-ceRNA network in human breast cancer / F. Conte, G. Fiscon, M. Chiara, T. Colombo, L. Farina, P. Paci. - In: PLOS ONE. - ISSN 1932-6203. - 12:2(2017 Jan), p. e0171661.e0171661.
open
Prodotti della ricerca::01 - Articolo su periodico
6
262
Article (author)
si
F. Conte, G. Fiscon, M. Chiara, T. Colombo, L. Farina, P. Paci
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/482188
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