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Amino Acids

, Volume 50, Issue 3–4, pp 421–438 | Cite as

A long non-coding RNA inside the type 2 transglutaminase gene tightly correlates with the expression of its transcriptional variants

  • Linda Minotti
  • Federica Baldassari
  • Marco Galasso
  • Stefano Volinia
  • Carlo M. Bergamini
  • Nicoletta Bianchi
Original Article

Abstract

The long non-coding RNAs (lncRNAs) are matter of intense investigation as potential regulators of gene expression. In the case of the transglutaminase 2 gene (TGM2) the databases of genome sequence indicate location of a lncRNA (LOC107987281) within the first intron. This lncRNA is 1000 bp long, arises from 2 exons and starts few nucleotides 3′ of the first splicing site of translated TGM2. We have analysed correlations between expression of LOC107987281 lncRNA and TGM2 mRNA by real-time PCR in K562 cell line untreated or treated with the anticancer drugs TPA (12-O-tetradecanoylphorbol-13-acetate), Docetaxel and Doxorubicin. In the treated cells the lncRNA increase follows the trend of TGM2 transcript. To validate this finding we used HumanExon1_0ST Affymetrix; chip data were background-adjusted, quantile-normalized and summarized using robust multi-array average analysis implemented in the R package. The probesets recognize sequences inside each exon, near intronic splicing sites and others located in the untranslated regions of TGM2 gene. The analysis of total RNA samples in GEO datasets from K562, HL-60, THP-1 and U937 cell lines, untreated or treated with TPA in replicated experiments confirmed our earlier results. These demonstrate correlation between LOC107987281 and TGM2 mRNA in the cell lines (K562, HL60 and THP-1) where increased levels of TGM2 mRNA are produced. Additional array study on 358 samples of several normal and paired tumor tissues leads to the same conclusions, indicating a correlation between full-length TGM2 mRNA and LOC107987281 lncRNA in relation to the development of several tumors.

Keywords

LOC107987281 Long non-coding RNA Transglutaminase 2 Alternative splicing transcript Transglutaminase 2 isoform 

Abbreviations

AD

Alzheimer’s disease

ATRA

All-trans-retinoic acid

DMSO

Dimethyl sulfoxide

GEO

Gene Expression Omnibus

HD

Huntington’s disease

HPRT1

Hypoxanthine phosphoribosyltransferase

lncRNA

Long non-coding RNA

miRNA

microRNA

NI

Normalized intensity

PLCδ1

Phospholipase Cδ1

RMA

Robust multi-array average

RT-qPCR

Reverse Transcription- quantitative Polymerase Chain Reaction

SI

Splicing index

SPSS

Statistical package for social science

TPA

12-O-Tetradecanoylphorbol-13-acetate

TGH

Transglutaminase 2 isoform AA1-548

TGH2

Transglutaminase 2 isoform AA1-349

TGM2

Transglutaminase 2 gene

tTGV1

tTG alternative splicing variant 1

tTGV2

tTG alternative splicing variant 2

Tg2

Type 2 transglutaminase

NT

Untreated

Notes

Acknowledgements

S.V. is supported by Associazione Italiana Ricerca sul Cancro AIRC (IG 17063); CMB is supported by FAR2017 (Unife).

Author contributions

LM carry out bioinformatic analysis, FB performed the experiments on culture cell lines, MG revised the manuscript critically and suggested some idea to improve the work, NB conceived the study. SV and CMB participated in financing and experimental design. NB, CMB, LM and SV carried it out and drafted the manuscript. All authors approved the final manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.

Ethical statement

The research has been performed on commercially available cell lines and taken advantage of data sets store in public databanks not involving Human Participants and/or Animals.

Supplementary material

726_2017_2528_MOESM1_ESM.docx (18 kb)
Supplementary material 1 (DOCX 18 kb)
726_2017_2528_MOESM2_ESM.tif (118 kb)
Suppl. Figure 1 Pattern of evolution divergence of LOC107987281 lncRNA. Cladogram from UCSC Genome Browser (http://genome.UCSC.edu). (TIFF 118 kb)
726_2017_2528_MOESM3_ESM.tif (799 kb)
Suppl. Figure 2 Sequence alignment of LOC107987281 lncRNA. This track shows multiple alignments of 100 vertebrate species in UCSC Genome Browser (http://genome.UCSC.edu). (TIFF 799 kb)
726_2017_2528_MOESM4_ESM.tif (969 kb)
Suppl. Figure 3 Sequence alignment of TGM2. This track shows multiple alignments of 100 vertebrate species in UCSC Genome Browser (http://genome.UCSC.edu). (TIFF 969 kb)

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Copyright information

© Springer-Verlag GmbH Austria, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Section of Anatomy and Histology, Department of Morphology, Surgery and Experimental MedicineUniversity of FerraraFerraraItaly
  2. 2.Section of Biochemistry, Molecular Biology and Medical Genetics, Department of Biomedical Sciences and Specialist SurgeryUniversity of FerraraFerraraItaly

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