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Biochim Biophys Acta Gen Subj. 2019 Feb;1863(2):491-501. doi: 10.1016/j.bbagen.2018.12.001. Epub 2018 Dec 5.

TRIM8-driven transcriptomic profile of neural stem cells identified glioma-related nodal genes and pathways.

Author information

1
Division of Medical Genetics, Fondazione IRCCS Casa Sollievo della Sofferenza, Viale Padre Pio, 71013, San Giovanni Rotondo, Foggia, Italy; Experimental and Regenerative Medicine, University of Foggia, Via A. Gramsci, 89/91, 71122, Foggia, Italy. Electronic address: s.venuto@operapadrepio.it.
2
Bioinformatics Unit, Fondazione IRCCS Casa Sollievo della Sofferenza, Viale Padre Pio, 71013, San Giovanni Rotondo, Foggia, Italy. Electronic address: s.castellana@css-mendel.it.
3
CEINGE Advanced Biotechnology, Department of Chemical Sciences, Federico II University, Via Gaetano Salvatore, 486, 80145, Napoli, Italy. Electronic address: montimar@unina.it.
4
U.O. Medicina Rigenerativa Ospedale Policlinico San Martino, Largo R. Benzi 10, 16132 Genova, Italy.
5
Bioinformatics Unit, Fondazione IRCCS Casa Sollievo della Sofferenza, Viale Padre Pio, 71013, San Giovanni Rotondo, Foggia, Italy. Electronic address: c.fusilli@css-mendel.it.
6
Division of Medical Genetics, Fondazione IRCCS Casa Sollievo della Sofferenza, Viale Padre Pio, 71013, San Giovanni Rotondo, Foggia, Italy. Electronic address: c.fusco@operapadrepio.it.
7
CEINGE Advanced Biotechnology, Department of Chemical Sciences, Federico II University, Via Gaetano Salvatore, 486, 80145, Napoli, Italy. Electronic address: pietro.pucci@unina.it.
8
U.O. Medicina Rigenerativa Ospedale Policlinico San Martino, Largo R. Benzi 10, 16132 Genova, Italy; Department of Experimental Medicine (DiMES), University of Genova, Via Leon Battista Alberti, 2, 16132 Genova, Italy. Electronic address: paolo.malatesta@unige.it.
9
Bioinformatics Unit, Fondazione IRCCS Casa Sollievo della Sofferenza, Viale Padre Pio, 71013, San Giovanni Rotondo, Foggia, Italy. Electronic address: t.mazza@operapadrepio.it.
10
Division of Medical Genetics, Fondazione IRCCS Casa Sollievo della Sofferenza, Viale Padre Pio, 71013, San Giovanni Rotondo, Foggia, Italy. Electronic address: g.merla@operapadrepio.it.
11
Division of Medical Genetics, Fondazione IRCCS Casa Sollievo della Sofferenza, Viale Padre Pio, 71013, San Giovanni Rotondo, Foggia, Italy. Electronic address: l.micale@operapadrepio.it.

Abstract

BACKGROUND:

We recently reported TRIM8, encoding an E3 ubiquitin ligase, as a gene aberrantly expressed in glioblastoma whose expression suppresses cell growth and induces a significant reduction of clonogenic potential in glioblastoma cell lines.

METHODS:

we provided novel insights on TRIM8 functions by profiling the transcriptome of TRIM8-expressing primary mouse embryonal neural stem cells by RNA-sequencing and bioinformatic analysis. Functional analysis including luciferase assay, western blot, PCR arrays, Real time quantitative PCR were performed to validate the transcriptomic data.

RESULTS:

Our study identified enriched pathways related to the neurotransmission and to the central nervous system (CNS) functions, including axonal guidance, GABA receptor, Ephrin B, synaptic long-term potentiation/depression, and glutamate receptor signalling pathways. Finally, we provided additional evidence about the existence of a functional interactive crosstalk between TRIM8 and STAT3.

CONCLUSIONS:

Our results substantiate the role of TRIM8 in the brain functions through the dysregulation of genes involved in different CNS-related pathways, including JAK-STAT.

GENERAL SIGNIFICANCE:

This study provides novel insights on the physiological TRIM8 function by profiling for the first time the primary Neural Stem Cell over-expressing TRIM8 by using RNA-Sequencing methodology.

KEYWORDS:

E3 ubiquitin ligase; STAT3; TRIM8; transcriptome

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