Genome-wide analysis of lncRNAs in 3'-untranslated regions: CR933609 acts as a decoy to protect the INO80D gene

Abstract

Long non‑coding RNAs (lncRNAs) have various functions, including chromatin remodeling and the regulation of gene expression at the transcriptional and post-transcriptional levels. However, few lncRNAs have been investigated comprehensively, with the majority being uncharacterized. In the present study, a bioinformatics pipeline was established to identify novel lncRNA sequences similar to the 3'-untranslated regions (3'‑UTRs) of protein-coding genes. These pairs of lncRNAs and coding genes contained the same microRNA (miRNA) target sites; the lncRNA CR933609 matched the 3'‑UTR of INO80 complex subunit D (INO80D) mRNA. The expression levels of CR933609 and INO80D were significantly decreased in non‑small cell lung cancer (NSCLC) and other cancer tissues. The expression levels of CR933609 and INO80D were decreased in CR933609-knockdown NSCLC cells, but only expression levels of INO80D decreased in INO80D knockdown cells. It was shown that there are independent promoters in CR933609 and INO80D. It was also found that the expression levels of INO80D were downregulated by endogenous miRNA‑5096 in A549 cells, but not in CR933609-overexpressing A549 cells. Furthermore, the lncRNA CR933609 acted as a decoy to protect INO80D from downregulation by miRNA‑5096 in NSCLC cells. A protocol was established to identify novel lncRNAs in the 3'‑UTR and the existence of novel lncRNAs was confirmed.

The expression signature of very long non-coding RNA in myalgic encephalomyelitis/chronic fatigue syndrome

“…Both EMX2OS and EMX2 RNAs have been detected in the central nervous system (CNS) tissues [ 22 ]. For CR933609, we have previously identified its role in protecting INO80D from downregulation by miRNA-5096 [ 23 ]. Since INO80D is a main component of the chromatin re-modeler INO80 complex which regulates cell glycolytic and respiratory capacities, CR933609 could be involved in maintaining metabolic stability [ 24 ].…”

Non-Coding RNAs and Nucleosome Remodeling Complexes: An Intricate Regulatory Relationship

“…The expression level of several subunits from SWI/SNF [88,89], ISWI [90], CHD [91,92], and INO80 [93,94] nucleosome remodeler families are regulated by miRNAs. Many of these interactions were initially identified through over-expression of characterized miRNAs and/or specific remodeler subunits in cancer types, or through correlated expression profiles with identified miRNAs [88][89][90][91][92][93][94]. For example, BAF subunit BAF60A expression is mis-regulated in two cancer types [88,89].…”

“…Cytoplasmic lncRNAs are primarily involved in post-transcriptional regulation of target mRNAs. The lncRNA CR993309 has been implicated as a post-transcriptional regulator of the INO80 complex subunit D (INO80D) in human epithelial cells [94]. This interaction was initially identified through a genome wide in silico approach looking for annotated lncRNAs with sequence complementarity to the 3'UTR of coding genes.…”

“…This interaction was initially identified through a genome wide in silico approach looking for annotated lncRNAs with sequence complementarity to the 3'UTR of coding genes. CR993309, overlapping the INO80D gene, bears 99% sequence homology to an approximately 9kb region of the 3'UTR of INO80D [94]. miRNA-5096 targets the 3'UTR of INO80D [94] and results in reduced expression of INO80D.…”

“…CR993309, overlapping the INO80D gene, bears 99% sequence homology to an approximately 9kb region of the 3'UTR of INO80D [94]. miRNA-5096 targets the 3'UTR of INO80D [94] and results in reduced expression of INO80D. Cells overexpressing CR993309 transfected with miRNA-5096 show an increase in INO80D expression, suggesting that CRR993309 may act as a 'miRNA sponge', or a decoy that sequesters miRNA-5096 to interfere with suppression of its intended target, INO80D [94].…”