miRNAsong: a web-based tool for generation and testing of miRNA sponge constructs in silico

Bárta, Tomáš; Pešková, Lucie; Hampl, Aleš

doi:10.1038/srep36625

Cited by 71 publications

(57 citation statements)

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“…In this regard, the RNA sponge length may form a short double‐stranded region that influenced the miR‐223 recognition . However, although there is no general rule regarding how many miRNA binding sites should be in a sponge RNA, its functionality would also depend on aspects such as the promoter used, the cell line and the expression of the target miRNA …”

Section: Discussionmentioning

confidence: 99%

“…17 However, although there is no general rule regarding how many miRNA binding sites should be in a sponge RNA, its functionality would also The normalized signal is expressed as mean ± SD of three independent experiments depend on aspects such as the promoter used, the cell line and the expression of the target miRNA. 18 After demonstrating that the sponge-vector expression pLVX-Sponge-223 4 with four perfectly complementary miR-223 binding sites in tandem did not have an inhibitory capacity for the function of miR-223, we decided to clone the same 60-bp region of the 3'-UTR of human MDR1/ABCB1 mRNA containing an imperfect binding site of miR-223 into the pLVX-shRNA2 backbone. However, the strategy of employing the same backbone to adopt the anti-miR-223 sponge represents a study limitation because this plasmid only expresses a fluorescent protein marker to monitor the transfection efficiency.…”

Section: Discussionmentioning

confidence: 99%

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A single miRNA and miRNA sponge expression system for efficient modulation of miR‐223 availability in mammalian cells

Huerta-Zavala¹,

Lopez-Castillejos²,

Requenez-Contreras³

et al. 2019

The Journal of Gene Medicine

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Background Hundreds of microRNAs (miRNAs), comprising small non‐coding RNAs of 20–24 nucleotides, have been discovered, although the entirety of their biological functions is poorly understood. Overexpression or suppression approaches are commonly performed to investigate the function of specific miRNAs. In the present study, we focused on generating a lentiviral vector‐based strategy that enables hsa‐miR‐223‐3p (miR‐223) overexpression and suppression in the target cells for functional analysis of this miRNA easily and rapidly. Methods The sequence that gives rise to miR‐223 and the sequence generating the sponge RNA with four binding sites for miR‐223 were cloned in pLVX‐shRNA2 vector. The functionality of the vector to overexpress miR‐223 was evaluated by quantitative reverse transcriptase‐polymerase chain reaction (qRT‐PCR) assays, whereas the post‐transcriptional regulation exerted by miR‐223 was evaluated by luciferase reporter assays in AD‐293 cells. The anti‐miR‐223 sponge activity with one binding site for miR‐223 (pmCherry‐anti‐miR‐223) was confirmed by qRT‐PCR and the restoration of its target (IKKα) was evaluated by western blot assays in Jurkat cells. Results The pLVX‐miR‐223 vector is functional for over‐expressing miR‐223 and regulates the mRNA of MDR1/ABCB1 at the post‐transcriptional level in AD‐293 cells. The anti‐miR‐223 sponge with one miR‐223 binding site efficiently modulates the miR‐223 availability and not the one with four sites. The over‐expression of anti‐miR‐223 correlated with a decrease in the levels of miR‐223 and, consequently, with an increase in the expression level of the IKKα protein in Jurkat cells. Conclusions This single miRNA and miRNA sponge expression system specifically alters the availability of miR‐223 in mammalian cells.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

A single miRNA and miRNA sponge expression system for efficient modulation of miR‐223 availability in mammalian cells

Huerta-Zavala¹,

Lopez-Castillejos²,

Requenez-Contreras³

et al. 2019

The Journal of Gene Medicine

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“…Recently, some tools have been developed, including spongeScan [20], miRNAsong [21], CircInteractome [22], miRNACancerMAP [23], and JAMI [24], to study miRNA sponges. Based on the sequence data of miRNAs and RNA transcripts, the first three web-based tools, spongeScan, miRNAsong and CircInteractome, regard RNA transcripts containing multiple miRNA binding sites as potential miRNA sponges.…”

Section: Discussionmentioning

confidence: 99%

“…Here, a miRNA sponge module is defined as a cluster of miRNA sponges. It has been shown that there is a great potential to reveal the biological mechanisms in cancer by studying miRNA sponge networks and modules [5,11,19], and the computational methods for identifying miRNA sponge networks and modules can help broaden our study of miRNA sponges and generate hypotheses for wet lab experiments.Recently, some tools have been developed, including spongeScan [20], miRNAsong [21], CircInteractome [22], miRNACancerMAP [23], and JAMI [24], to study miRNA sponges. Based on the sequence data of miRNAs and RNA transcripts, the first three web-based tools, spongeScan, miRNAsong and CircInteractome, regard RNA transcripts containing multiple miRNA binding sites as potential miRNA sponges.…”

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confidence: 99%

miRsponge: an R/Bioconductor package for the identification and analysis of miRNA sponge interaction networks and modules

Zhang

Liu

et al. 2018

Preprint

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BackgroundA microRNA (miRNA) sponge is an RNA molecule with multiple tandem miRNA response elements that can sequester miRNAs from their target mRNAs. Despite growing appreciation of the importance of miRNA sponges, our knowledge of their complex functions remains limited. Moreover, there is still a lack of miRNA sponge research tools that help researchers to quickly compare their proposed methods with other methods, apply existing methods to new datasets, or select appropriate methods for assisting in subsequent experimental design. ResultsTo fill the gap, we present an R/Bioconductor package, miRspongeR, for simplifying the procedure of identifying and analyzing miRNA sponge interaction networks and modules. It provides seven popular methods and an integrative method to identify miRNA sponge interactions. Moreover, it supports the validation of miRNA sponge interactions and the identification of miRNA sponge modules, as well as functional enrichment and survival analysis of miRNA sponge modules. ConclusionsThis package enables researchers to quickly evaluate their new methods, apply existing methods to new datasets, and consequently speed up miRNA sponge research. Keywords miRNA -ceRNA -miRNA sponge -miRNA sponge interaction networks -miRNA sponge modules -human breast invasive carcinoma Background MicroRNAs (miRNAs) are small non-coding RNAs with ~22 nucleotides. They usually induce repression or translational inhabitation of target genes through partial -3 -complementarities with multiple miRNA response elements (MREs) of the target RNA transcripts [1]. Previous studies [2, 3] have shown that miRNAs are involved in a broad range of biological processes, such as cell cycle control, cell apoptosis, cell differentiation and a diverse range of human cancers. The competing endogenous RNA (ceRNA) hypothesis [4] considers that all types of coding and non-coding RNA transcripts may crosstalk with each other by sharing common miRNAs. By competing with each other, those ceRNAs (also known as miRNA sponges or decoys), including long non-coding RNAs (lncRNAs), pseudogenes, mRNAs and circular RNAs (circRNAs), can release parental target mRNAs from miRNAs' control [5]. The ceRNA hypothesis challenges the traditional knowledge that coding RNAs only act as targets of miRNAs, and it provides a starting point for the investigation of the biological functions and mechanisms of miRNA sponges. Recently, several lncRNAs, pseudogenes, circRNAs and mRNAs acting as miRNA sponges have been experimentally identified and confirmed, together with their important biological functions. For example, linc-MD1, a muscle-specific lncRNA, activates muscle-specific gene expression by regulating the expression of MAML1 and MEF2C via sponging miR-133 and miR-135 [6]. PTENP1, a pseudogene of the PTEN tumor suppression gene, can act as a sponge of PTEN-targeting miRNAs to play a growth-suppressive role [7]. As for circRNAs, CDR1as/ciRS-7 is encoded in the genome antisense to the human CDR1 (gene) locus, and affects the activity of miR-7 target genes...

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“…In the first category [9, 10], similar to miRNA target recognition, the principle of complementary base-pairing is assumed when recognizing miRNA sponges. In other words, it is assumed that there is an interaction between the 5′-end of an miRNA called the ‘seed region’ and the sequence of the miRNA sponge.…”

Section: Introductionmentioning

confidence: 99%

Inferring miRNA sponge co-regulation of protein-protein interactions in human breast cancer

Zhang

Liu

et al. 2017

BMC Bioinformatics

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BackgroundRecent studies have shown that the crosstalk between microRNA (miRNA) sponges plays an important role in human cancers. However, the co-regulation roles of miRNA sponges in protein-protein interactions (PPIs) are still unknown.ResultsIn this study, we propose a multi-step method called miRSCoPPI to infer miRNA sponge co-regulation of PPIs. We focus on investigating breast cancer (BRCA) related miRNA sponge co-regulation, by integrating heterogeneous data, including miRNA, long non-coding RNA (lncRNA) and messenger RNA (mRNA) expression data, experimentally validated miRNA-target interactions, PPIs and lncRNA-target interactions, and the list of breast cancer genes. We find that the inferred BRCA-related miRSCoPPI network is highly connected and scale free. The top 10% hub genes in the BRCA-related miRSCoPPI network have potential biological implications in breast cancer. By utilizing a graph clustering method, we discover 17 BRCA-related miRSCoPPI modules. Through pathway enrichment analysis of the modules, we find that several modules are significantly enriched in pathways associated with breast cancer. Moreover, 10 modules have good performance in classifying breast tumor and normal samples, and can act as module signatures for prognostication. By using putative computationally predicted miRNA-target interactions, we have consistent results with those obtained using experimentally validated miRNA-target interactions, indicating that miRSCoPPI is robust in inferring miRNA sponge co-regulation of PPIs in human breast cancer.ConclusionsTaken together, the results demonstrate that miRSCoPPI is a promising tool for inferring BRCA-related miRNA sponge co-regulation of PPIs and it can help with the understanding of the co-regulation roles of miRNA sponges on the PPIs.Electronic supplementary materialThe online version of this article (doi:10.1186/s12859-017-1672-2) contains supplementary material, which is available to authorized users.

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miRNAsong: a web-based tool for generation and testing of miRNA sponge constructs in silico

Cited by 71 publications

References 50 publications

A single miRNA and miRNA sponge expression system for efficient modulation of miR‐223 availability in mammalian cells

A single miRNA and miRNA sponge expression system for efficient modulation of miR‐223 availability in mammalian cells

miRsponge: an R/Bioconductor package for the identification and analysis of miRNA sponge interaction networks and modules

Inferring miRNA sponge co-regulation of protein-protein interactions in human breast cancer

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