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

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.

Dysregulation of Transglutaminase type 2 through GATA3 defines aggressiveness and Doxorubicin sensitivity in breast cancer

“…The TGM2 gene expression analysis of these datasets was performed by normalizing signal intensity (NI) for each specific probe of the variants and comparing them among the samples, as described by Minotti et al [28].…”

IV. Ikergazte. Nazioarteko ikerketa euskaraz. Kongresuko artikulu bilduma. Zientziak eta Natura Zientzia

“…Emaitza hauek TGM2 geneak intsulinaren jariapenean, eta ondorioz, pankreako beta zelulen ohiko funtzioan daukan garrantzia erakusten dute, TGM2 genearen erregulazio ondo ulertzea ezinbestekoa izanik. Berriki, zenbait zelula lerrotan gauzaturiko ikerketetan, TGM2 genearen adierazpenarekin korrelazio zuzena duen RNA luze ez-kodetzaile (lncRNA; ingelesez long noncoding RNA) bat (LOC107987281) identifikatu da (Minotti et al, 2018). LOC107987281 lncRNA, TGM2ren lehenengo introitik transkribatzen da eta 1000 nukleotidoz osatua dago (Minotti et al, 2018).…”

“…Berriki, zenbait zelula lerrotan gauzaturiko ikerketetan, TGM2 genearen adierazpenarekin korrelazio zuzena duen RNA luze ez-kodetzaile (lncRNA; ingelesez long noncoding RNA) bat (LOC107987281) identifikatu da (Minotti et al, 2018). LOC107987281 lncRNA, TGM2ren lehenengo introitik transkribatzen da eta 1000 nukleotidoz osatua dago (Minotti et al, 2018). LncRNA honek nukleotido bakarreko polimorfismo (SNP: ingelesez single nucleotide polymorphism) bat dauka bere lehenengo exoian, TGM2 gene kodetzailean intronikoa dena.…”

Inhibition of the lncRNA Coded within Transglutaminase 2 Gene Impacts Several Relevant Networks in MCF-7 Breast Cancer Cells

“…The expression of TG2-lncRNA is under the control of the same promoter of TGM2 and is modulated by drugs capable of increasing the levels of TG2 protein. For example, all-trans retinoic acid (ATRA) is used for the treatment of promyelocytic leukaemia HL-60 cells [7] and its effects on gene expression were also observed in human leukemic NB4 and neuroblastoma SK-N-SH cell lines [1]. In this context, its nuclear location and the ability to bind regulatory factors suggest a role as a possible transcriptional modulator [7].…”