lnCeDB: Database of Human Long Noncoding RNA Acting as Competing Endogenous RNA

Abstract

Long noncoding RNA (lncRNA) influences post-transcriptional regulation by interfering with the microRNA (miRNA) pathways, acting as competing endogenous RNA (ceRNA). These lncRNAs have miRNA responsive elements (MRE) in them, and control endogenous miRNAs available for binding with their target mRNAs, thus reducing the repression of these mRNAs. ln Ce DB provides a database of human lncRNAs (from GENCODE 19 version) that can potentially act as ceRNAs. The putative mRNA targets of human miRNAs and the targets mapped to AGO clipped regions are collected from TargetScan and StarBase respectively. The lncRNA targets of human miRNAs (up to GENCODE 11) are downloaded from miRCode database. miRNA targets on the rest of the GENCODE 19 lncRNAs are predicted by our algorithm for finding seed-matched target sites. These putative miRNA-lncRNA interactions are mapped to the Ago interacting regions within lncRNAs. To find out the likelihood of an lncRNA-mRNA pair for actually being ceRNA we take recourse to two methods. First, a ceRNA score is calculated from the ratio of the number of shared MREs between the pair with the total number of MREs of the individual candidate gene. Second, the P-value for each ceRNA pair is determined by hypergeometric test using the number of shared miRNAs between the ceRNA pair against the number of miRNAs interacting with the individual RNAs. Typically, in a pair of RNAs being targeted by common miRNA(s), there should be a correlation of expression so that the increase in level of one ceRNA results in the increased level of the other ceRNA. Near-equimolar concentration of the competing RNAs is associated with more profound ceRNA effect. In lnCeDB one can not only browse for lncRNA-mRNA pairs having common targeting miRNAs, but also compare the expression of the pair in 22 human tissues to estimate the chances of the pair for actually being ceRNAs. Availability: Downloadable freely from http://gyanxet-beta.com/lncedb/.

Effect of the LncRNA GAS5-MiR-23a-ATG3 Axis in Regulating Autophagy in Patients with Breast Cancer

“…It has been reported that lncRNAs affect post-transcriptional regulation by interfering with miRNA pathways, acting as ceRNAs [45] . Our study also revealed that GAS5 can be used as a "molecular sponge" to block and bind miR-23a, thereby positively modulating the miR23a targeted autophagy-related gene ATG3.…”

Basic biology and therapeutic implications of lncRNA

“…In turn, lncRNAs have been shown to bind both miRNA themselves and miRNA binding sites on their target mRNAs, thus modulating miRNA activity (Fig.1K). Competing endogenous lncRNAs (termed ceRNAs [20]), which act as miRNA sponges, include, for example lncRNA CHRF, which has been shown to bind miR-489, reducing its availability for downregulating Myd88 mRNA [70]. In other examples, linc ROR blocks miR-145 [71]; lncRNA PTENP1 modulates endogenous PTEN transcript levels by acting as a molecular sponge for PTEN-targeting miRNAs [72]; linc-MD1 is a muscle-specific lncRNA which activates the expression of MAML1 and MEF2C by sponging up miR-133 [73].…”

Identifying and annotating human bifunctional RNAs reveals their versatile functions

“…The 132 identified bifunctional RNAs were mapped to the ceRNA candidates documented in the lnCeDB database (Das et al, 2014) and 26 bifunctional RNAs were matched. In summary, those 26 bifunctional RNAs can act as ceRNAs to compete with related RNAs for 963 targeting miRNAs, which may result in changes in expression levels of corresponding RNAs.…”

“…We also examined the expression correlatio between bifunctional RNAs and their targeting miRNAs using miRGator V3.0 (Cho et al, 2013) in different cancer and normal tissues. To interrogate whether bifunctional RNAs could act as ceRNAs to regulate the expression of relevant genes, we checked their existence in the ceRNA candidates cataloged in lnCeDB database (Das et al, 2014). The cancer related genes of diverse human cancers from the databases of NCG4.0 , TSGene (Zhao et al, 2013) and two previous studies about human pan-cancer (Kandoth et al, 2013;Vogelstein et al, 2013) were collected as well.…”