Identification of new SOX2OT transcript variants highly expressed in human cancer cell lines and down regulated in stem cell differentiation

Mol Biol Rep. 2016 Feb;43(2):65-72. doi: 10.1007/s11033-015-3939-x. Epub 2015 Dec 24.

Abstract

Long non-coding RNAs are manifested as a new paradigm of molecular effectors in a wide range of human diseases. Human SOX2 overlapping transcript (SOX2OT) gene can generate six lncRNA transcript variants which are functionally assumed to be correlated with cellular differentiation and carcinogenesis. However, the circumstances determining expressional and functional differences between SOX2OT transcript variants remain to be explored. Here, we studied the expression of all SOX2OT transcript variants specifically in five human cancer cell lines by real-time RT-PCR. Changes of the new SOX2OT transcript variants expression were measured during the NT2 teratocarcinoma cell line neuronal-like differentiation and were compared to pluripotency regulators, SOX2 and OCT4A gene expressions. Surprisingly, we identified two new SOX2OT transcripts, named SOX2OT-7, SOX2OT-8 which lack exon 8. We discovered that beside active proximal and distal SOX2OT promoters, different cancer cell lines express high levels of some SOX2OT transcript variants differentially by alternative splicing. Significantly, both SOX2OT-7 and SOX2OT-8 are highly expressed in human cancer cell lines coinciding with SOX2, one of the pluripotency regulators. Our results revealed that SOX2OT-7 is almost the most abundant form of SOX2OT transcript variants in the examined cancer cell lines particularly in NT2 teratocarcinoma cell line where its expression falls upon neuronal-like differentiation similar to SOX2 and OCT4A. We suggest that at least some of SOX2OT transcripts are significantly associated with cancer and stem cell related pathways.

Keywords: Carcinogenesis; Long non-coding RNA; Neuronal like differentiation; SOX2 overlapping transcript.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing*
  • Cell Differentiation
  • Cell Line, Tumor
  • Exons
  • HeLa Cells
  • Hep G2 Cells
  • Humans
  • Introns
  • MCF-7 Cells
  • Neurons / cytology
  • Neurons / metabolism*
  • Octamer Transcription Factor-3 / genetics*
  • Octamer Transcription Factor-3 / metabolism
  • RNA Isoforms / genetics*
  • RNA Isoforms / metabolism
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism
  • Real-Time Polymerase Chain Reaction
  • SOXB1 Transcription Factors / genetics*
  • SOXB1 Transcription Factors / metabolism
  • Signal Transduction
  • Stem Cells / cytology
  • Stem Cells / metabolism

Substances

  • Octamer Transcription Factor-3
  • POU5F1 protein, human
  • RNA Isoforms
  • RNA, Long Noncoding
  • SOX2 protein, human
  • SOXB1 Transcription Factors
  • long non-coding RNA Sox2ot, human