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miRNA-mediated competing endogenous RNAs (ceRNAs) networks - (Dec/04/2013 )

Competing endogenous RNAs (ceRNAs) hypothesis: ceRNAs regulate other RNA transcripts (e.g., PTEN) by competing for shared microRNAs. 
 
They are playing important roles in developmental, physiological and pathological processes, such as cancer. (Salmena et al. 2011 Cell). 
 
Multiple classes of ncRNAs (lncRNAs, circRNAs, pseudogenes) and protein-coding mRNAs function as key ceRNAs and  to regulate the expression of mRNAs in plants and mammalian cells (see below references).
 
 
ceRNA resoures:  
1. ceRNABase:  identified ~200,000 (P<0.05) and ~10,000 (FDR<0.05) ceRNA pairs from CLIP-supported miRNA target sites.
provided ceRNAFunction tool to predict the functions of lncRNAs and protein-coding genes from ceRNA regulatory networks. website: http://starbase.sysu.edu.cn/mrnaCeRNA.php
 
2. Competing endogenous RNA database: predicted ceRNA candidates from genome. website: http://www.oncomir.umn.edu/cefinder/
 
 
ceRNA References:
  1. HMGA2 functions as a competing endogenous RNA to promote lung cancer progression. Nature 2013, Dec 5.
  2. starBase v2.0: decoding miRNA-ceRNA, miRNA-ncRNA and protein–RNA interaction networks from large-scale CLIP-Seq data. Nucleic Acids Res. 2013 Dec 1.
  3. A long noncoding RNA controls muscle differentiation by functioning as a competing endogenous RNA. Cell. 2011 Oct 14;147(2):358-69
  4. A coding-independent function of gene and pseudogene mRNAs regulates tumour biology. Nature. 2010 Jun 24;465(7301):1033-8.
  5. A ceRNA hypothesis: the Rosetta Stone of a hidden RNA language? Cell. 2011 Aug 5;146(3):353-8.
  6. Circular RNAs are a large class of animal RNAs with regulatory potency. Nature. 2013 Mar 21;495(7441):333-8.
  7. Natural RNA circles function as efficient microRNA sponges.Nature. 2013 Mar 21;495(7441):384-8.
  8. Endogenous miRNA sponge lincRNA-RoR regulates Oct4, Nanog, and Sox2 in human embryonic stem cell self-renewal. Dev Cell. 2013 Apr 15;25(1):69-80.
  9. The Imprinted H19 LncRNA Antagonizes Let-7 MicroRNAs. Mol Cell. 2013 Oct 10;52(1):101-12.

-zhxq09-

A Nature paper has described ceRNA interactions between HMGA2 and TGFBR3. They show that Hmga2 promotes lung cancer progression in mouse and human cells by operating as a competing endogenous RNA (ceRNA) for the let-7 microRNA (miRNA) family.

reference: HMGA2 functions as a competing endogenous RNA to promote lung cancer progression (Nature, 2013 Dec 5)

 

ceRNABase can captured the above-mentioned HMGA2-TGFBR3 ceRNA pairs.

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zhxq09 on Mon Dec 9 10:40:02 2013 said:

A Nature paper has described ceRNA interactions between HMGA2 and TGFBR3. They show that Hmga2 promotes lung cancer progression in mouse and human cells by operating as a competing endogenous RNA (ceRNA) for the let-7 microRNA (miRNA) family.

reference: HMGA2 functions as a competing endogenous RNA to promote lung cancer progression (Nature, 2013 Dec 5)

 

ceRNABase can captured the above-mentioned HMGA2-TGFBR3 ceRNA pairs.

ceRNABase also recaptured PTEN-TNRC6A, PTEN-TNRC6B, PTEN-ZEB2, PTEN-NRAS, PTEN-CNOT6L, PTEN-CCDC6, PTEN-LRCH1, PTEN-JARID2, PTEN-SERINC1, PTEN-KLF6, PTEN-MBNL1 etc. ceRNA pairs that reported by three Cell papers(Tay et al. Cell. 2011;147:344-57., Karreth et al. Cell. 2011;147:382-95., Sumazin et al. Cell. 2011;147:370-81.).

 

You can enter other Cancer-driver genes (e.g. PTEN, APC) to search cancer-associated ceRNAs.

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A ceRNA review paper has been published in Nature Journal. 
 
Tay Y, Rinn J, Pandolfi PP. The multilayered complexity of ceRNA crosstalk and competition. Nature. 2014 Jan 16;505(7483):344-52. 
 
Abstract

Recent reports have described an intricate interplay among diverse RNA species, including protein-coding messenger RNAs and non-coding RNAs such as long non-coding RNAs, pseudogenes and circular RNAs. These RNA transcripts act as competing endogenous RNAs (ceRNAs) or natural microRNA sponges - they communicate with and co-regulate each other by competing for binding to shared microRNAs, a family of small non-coding RNAs that are important post-transcriptional regulators of gene expression. Understanding this novel RNA crosstalk will lead to significant insight into gene regulatory networks and have implications in human development and disease.

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ceRNABase have constructed pan-cancer ceRNA networks from tumor miRNA and mRNA expression profiles (TCGA 14 cancer types with >6000 tumor and normal samples). 
 
For example: known PTEN-ZEB2 ceRNA interactions can be supported in 13 cancer types.
 

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