1. miRNA-Target

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The "miRNA-Target" module provides the most comprehensive miRNA-mRNA, miRNA-lncRNA, miRNA-pseudogene, miRNA-circRNA, and miRNA-sncRNA interaction networks in different cell lines, tissues in different conditions. Here, we provide two examples to show how to use the module to explore the miRNA-ncRNA and miRNA-RNA interactions supported by Ago CLIP-seq experiments.

 

1-1 How many mRNAs could interact with hsa-miR-21-5p?

 

A particular miRNA can pair specifically with several target mRNAs performing different biological functions. How could we know the mRNAs that interact with the interested miRNA? Here, take "hsa-miR-21-5p" (in human) which has been reported to interact with PDCD4 as an example (Fig.1-1a):

 

 

1-2 How many miRNAs may target PDCD4 gene?

 

A single mRNA can be recognized and regulated by multiple miRNAs. In most cases, we want to figure out our target gene can be potentially regulated by how many miRNAs. Take PDCD4 gene (in human) as an example (Fig.1-2):

 

 

1-3 How many miRNAs may target circRNA HIPK3?

 

The identification and characterization of circRNA have recently reshaped the RNA world. And the biological functions of cirRNAs suggest a novel mechanism for regulating microRNAs. Here, we instance HIPK3 (in human), which is directly binds to miR-124 and inhibits miR-124 activity, to explore miRNA-cirRNA interactions (Fig.1-3):

 

2. Degradome-RNA

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The "Degradome-RNA" module provides a comprehensive means of analyzing patterns of RNA degradation and has 2 sub-modules, including miRNA-mRNA and miRNA-ncRNA. Here, we give two examples to show how to use the module to explore the cleavage-mediated miRNA-mRNA and miRNA-ncRNA interactions supported by degradome-seq experiments.

 

2-1 Which mRNAs are natural targets of miR-196-directed cleavage?

 

A microRNA usually can exert post-transcriptional control over a broad set of cellular mRNAs. Here, we take "miR-196" (in human) that has been reported to interact with HOXB8 as an example to explore miRNA-mRNA interactions (Fig.2-1a):

 

2-2 How many miRNAs may mediate the degradation of MYB33 gene?

 

In plants, miRNAs usually cause targeted gene scilencing by directing the cleavage of targets. Here, we take "MYB33" (in A. thaliana) as an example to study cleavage-mediated miRNA-mRNA interactions (Fig.2-2a):

 

3. RNA-RNA

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The "RNA-RNA" module provides the comprehensive prediction of RNA–RNA interactions (RRI) between candidate ncRNAs and their targets to understand the role of the RNA. And there are 4 sub-modules, including mRNA-RNA, lncRNA-RNA, pseudogene-RNA, sncRNA-RNA. Here, we give an example to show how to use the module to explore the lncRNA-RNA interactions identified from high-throughput sequencing data of RNA-RNA interactome.

 

3-1 How many RNAs could H19 interact with?

 

lncRNAs have well established functions and much remains to be done towards decipherment of their biological roles. One of the least studied aspects of lncRNAs biology is their engagement in gene expression regulation through RNA-RNA interactions. We instance H19 thath has been reported to interact with DICER to explore lncRNA-RNA interaction network (Fig.3-1a).

 

4. ceRNA-Network

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The "ceRNA-Network" module provides 3 sub-modules, including mRNA-ceRNA, lncRNA-ceRNA and pseudogene-ceRNA, which are used to visualize the crosstalk between mRNAs, lncRNAs, transcribed pseudogenes and their parent genes by competitive binding of microRNAs respectively. Here, we use an example to introduce how to use the module to study the mRNA-ceRNA interactions supported by CLIP-seq data.

 

4-1 What are the ceRNA interaction networks of PTEN?

 

Crosstalk between RNAs mediated by shared miRNAs represents a novel layer of gene regulation, which plays important roles in cellular scenarios. Study the PTEN-centered (in human) ceRNA networks as an example to explore the module (Fig.4-1).

 

5. RBP-Target

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The "RBP-Target" module provides the most integrated RBP-ncRNA interactions for various cell types that are presently available. There are 5 sub-modules in this module, including RBP-mRNA, RBP-lncRNA, RBP-pseudogene, RBP-circRNA as well as RBP-sncRNA. Accompanied with shRNA screen data and convinced interactions of RBP-RNA, we systematically explored the response of RBP targets upon RBP-knockdown conditions in K562 and HepG2 cell lines. As an example, we study RBP-mRNA interactions to explore the RBP-Target module.

 

5-1 How many RBPs could regulate TP53?

 

RBPs are crucial functional components of the molecular machineries involved in posttranscriptional events, such as premRNA splicing, mRNA editing. We navigate the reported CBX7-TP53 (in human) interactions as an example (Fig.5-1a):

 

6. RBP-Motif

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The "RBP-Motif" module provides insight into the function and evolution of both RBPs and their binding sites. We present a systematic analysis of the RNA motifs recognized by RNA-binding proteins. Here, we study RBP-mRNA interactions as an example to illustrate the RBP-Motif module.

 

6-1 What are the motifs of IGF2BP2?

 

RBPs are crucial functional components of the molecular machineries involved in posttranscriptional events, such as premRNA splicing, mRNA editing. Sequence-specific associations between RBPs and their RNA targets are typically regulated by one or more motifs, however, few of them have been studied in detail. We identify the motifs of IGF2BP2 (in human) as an example (Fig.6-1):

 

7. RBP-Disease

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The "RBP-Disease" module provides visualization of the relationships between RBP and somatic gene mutations in 44 tissues and 366 diseases. Here is an example using the module to explain the potential connections between RBP-RNA interactions and its related diseases.

 

7-1 How are the correlations between RBP-BRCA1 interactions and somatic mutations?

 

RBPs are a class of post-transcriptional regulatory molecules which are increasingly documented to accumulate functionally impactful mutations in cancer genomes. However, our current understanding of their relationships with somatic mutations is limited. Using the RBP-Disease module, we can explore the deeper connections between RBP-BRCA1 interactions and somatic mutations in human diseases. Take the reported DHX9-BRCA1 interactions as an example (Fig.7-1a).

 

8. Pathway

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The "Pathway" module provides the interactions of miRNA-targets by intersecting the predicting target sites of miRNAs with binding sites of Ago protein, which were derived from CLIP-seq data. There are 4 sub-modules, including mirTarPathway, rbpTarPathway, rnaTarPathway, ceRnaPathway. To study the interactions of miRNA and targets, we give the following example.

 

8-1 What are the potential biological roles of hsa-let-7a-5p?

 

RBPs has diverse cellular post-transcriptional regulatory functions. Pathway analysis of RBPs can reveal their potential biological roles. We do the enrichment analysis of hsa-let-7a-5p in KEGG pathways (Fig.8-1).

 

9. Pan-Cancer

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The "Pan-Cancer" module provides comprehensive Pan-Cancer Networks of lncRNAs, miRNAs, pseudogenes, snoRNAs and RNA-binding proteins (RBPs) by analyzing their expression profiles across 32 cancer types ( ~9900 miRNA-seq and ~10,000 samples) integrated from TCGA project via Genomic Data Commons Data Portal. There are 6 cancer-related services, including miRNA Differential Expression, miRNA survival Analysis, miRNA-Target CoExpression, Gene Differential Expression, Gene Survival Analysis and RNA-RNA CoExpression. Here, we introduce the Pan-Cancer analysis platform with 4 examples to explore the Pan-Cancer network of miRNA-lncRNA, miRNA-pseudogene, miRNA-sncRNA and miRNA-mRNA interactions.

 

9-1 What is the expression pattern of miR-34a in cancer?

 

An increasing number of studies have identified miRNAs as potential biomarkers for human cancer diagnosis, prognosis and therapeutic targets or tools, which needs further investigation and validation. MiRNAs may function as either oncogenes or tumor suppressors under certain conditions. Take "miR-34a" as an example (Fig.9-1a~b).

 

 

9-2 What is the relationship between hsa-mir-21-5p and PDCD4 in colorectal cancer?

 

Abnormalities in non-coding genes, including miRNAs, can determine biological alterations in tumor cells to execute the invasion-metastasis cascade. We seek to investigate the relationship between miR-21 ang PDCD4 in colorectal cancer regulation (Fig.9-2a~b).

 

 

9-3 What is the association between HOTAIR expression and survival rates in Adrenocortical Carcinoma?

 

LncRNAs have emerged as primary regulators of carcinogenesis. Thus, lncRNAs may represent the novel prognostic and diagnostic markers of cancer, in addition to being the potential therapeutic targets. Here, we use "Gene Survival Analysis" module to explore overall survival rates in patients with Adrenocortical Carcinoma according to high or low HOTAIR expression levels (Fig.9-3a~b).

 

 

9-4 What is the correlation between IGF2BP1 and MYC in ovarian cancer?

 

Intermolecular RNA-RNA interactions are used by many noncoding RNAs (ncRNAs) to achieve their diverse functions. We develop the "RNA-RNA CoExpression" module to systematically analyze RNA-RNA interactions across 32 types of cancers and apply it to explore IGF2BP1 and MYC interactions in ovian cancer (Fig.9-4a~b).

 

10. Web API

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In the "Web API" module, we provide the direct programmatic access to all regulatory data stored within the server. This enables you to easily access data from your favorite programming language, such as Shell, Python, or Perl.

 

Here we use curl (command line tool) for communicating with the ENCORI APIs.

 

You can click "Web API" for more examples.

11. Tutorial PDF

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Open Tutorial.pdf