DDX5/p68 associated lncRNA LOC284454 is differentially expressed in human cancers and modulates gene expression

RNA Biol. 2018 Feb 1;15(2):214-230. doi: 10.1080/15476286.2017.1397261. Epub 2017 Dec 11.

Abstract

Long non-coding RNAs (lncRNAs) are emerging as important players in regulation of gene expression in higher eukaryotes. DDX5/p68 RNA helicase protein which is involved in splicing of precursor mRNAs also interacts with lncRNAs like, SRA and mrhl, to modulate gene expression. We performed RIP-seq analysis in HEK293T cells to identify the complete repertoire of DDX5/p68 interacting transcripts including 73 single exonic (SE) lncRNAs. The LOC284454 lncRNA is the second top hit of the list of SE lncRNAs which we have characterized in detail for its molecular features and cellular functions. The RNA is located in the same primary transcript harboring miR-23a∼27a∼24-2 cluster. LOC284454 is a stable, nuclear restricted and chromatin associated lncRNA. The sequence is conserved only in primates among 26 different species and is expressed in multiple human tissues. Expression of LOC284454 is significantly reduced in breast, prostate, uterus and kidney cancer and also in breast cancer cell lines (MCF7 and T47D). Global gene expression studies upon loss and gain of function of LOC284454 revealed perturbation of genes related to cancer-related pathways. Focal adhesion and cell migration pathway genes are downregulated under overexpression condition, and these genes are significantly upregulated in breast cancer cell lines as well as breast cancer tissue samples suggesting a functional role of LOC284454 lncRNA in breast cancer pathobiology.

Keywords: Cancer; DDX5/p68 RNA helicase; LOC284454; Long non-coding RNA; gene expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • DEAD-box RNA Helicases / genetics*
  • Down-Regulation
  • Female
  • Gene Expression Profiling / methods*
  • Gene Expression Regulation, Neoplastic
  • HEK293 Cells
  • Humans
  • MCF-7 Cells
  • Male
  • Neoplasms / genetics*
  • Oligonucleotide Array Sequence Analysis
  • RNA, Long Noncoding / genetics*
  • Sequence Analysis, RNA
  • Signal Transduction

Substances

  • RNA, Long Noncoding
  • Ddx5 protein, human
  • DEAD-box RNA Helicases

Grants and funding

M.R.S. Rao thanks Department of Science and Technology, Government of India for J.C. Bose and SERB Distinguished Fellowships and this work was financially supported by Department of Biotechnology, Govt. of India [Grant Number BT/01/COE/07/09].