Dataset Information

Chemoresistance Mediated by ceRNA Networks Associated With the PVT1 Locus.

ABSTRACT: Competitive endogenous RNA (ceRNA) networks have emerged as critical regulators of carcinogenesis. Their activity is mediated by various non-coding RNAs (ncRNAs), including long non-coding RNAs and microRNAs, which competitively bind to targets, thereby modulating gene expression and activity of proteins. Of particular interest, ncRNAs encoded by the 8q24 chromosomal region are associated with the development and progression of several human cancers, most prominently lncPVT1. Chemoresistance presents a significant obstacle in the treatment of cancer and is associated with dysregulation of normal cell processes, including abnormal proliferation, differentiation, and epithelial-mesenchymal transition. CeRNA networks have been shown to regulate these processes via both direct sponging/repression and epigenetic mechanisms. Here we present a review of recent literature examining the contribution of ncRNAs encoded by the PVT1 locus and their associated ceRNA networks to the development of resistance to common chemotherapeutic agents used to treat human cancers.

SUBMITTER: Ogunwobi OO

PROVIDER: S-EPMC6718704 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Chemoresistance Mediated by ceRNA Networks Associated With the PVT1 Locus.

Ogunwobi Olorunseun O OO Kumar Adithya A

Frontiers in oncology 20190827

Competitive endogenous RNA (ceRNA) networks have emerged as critical regulators of carcinogenesis. Their activity is mediated by various non-coding RNAs (ncRNAs), including long non-coding RNAs and microRNAs, which competitively bind to targets, thereby modulating gene expression and activity of proteins. Of particular interest, ncRNAs encoded by the 8q24 chromosomal region are associated with the development and progression of several human cancers, most prominently lncPVT1. Chemoresistance pre ...[more]

PMID: 31508377

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Project description: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.

Dataset Information

Chemoresistance Mediated by ceRNA Networks Associated With the PVT1 Locus.

Publications

Chemoresistance Mediated by ceRNA Networks Associated With the PVT1 Locus.

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