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

Int J Oncol. 2018 Jul;53(1):417-433. doi: 10.3892/ijo.2018.4398. Epub 2018 May 8.

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.

MeSH terms

  • 3' Untranslated Regions / genetics
  • A549 Cells
  • ATPases Associated with Diverse Cellular Activities
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Chromatin Assembly and Disassembly / genetics*
  • Computational Biology
  • DNA Helicases / genetics*
  • DNA-Binding Proteins
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Lung Neoplasms
  • MicroRNAs / genetics
  • Open Reading Frames / genetics
  • RNA, Long Noncoding / genetics*

Substances

  • 3' Untranslated Regions
  • DNA-Binding Proteins
  • MicroRNAs
  • RNA, Long Noncoding
  • ATPases Associated with Diverse Cellular Activities
  • DNA Helicases
  • INO80 protein, human