Human germ/stem cell-specific gene TEX19 influences cancer cell proliferation and cancer prognosis

Vicente Planells-Palop, Ali Hazazi, Julia Feichtinger, Jana Jezkova, Gerhard Thallinger, Naif O Alsiwiehri, Mikhlid Almutairi, Lee Parry, Jane A Wakeman, Ramsay J McFarlane

Research output: Contribution to journalArticle

Abstract

BACKGROUND: Cancer/testis (CT) genes have expression normally restricted to the testis, but become activated during oncogenesis, so they have excellent potential as cancer-specific biomarkers. Evidence is starting to emerge to indicate that they also provide function(s) in the oncogenic programme. Human TEX19 is a recently identified CT gene, but a functional role for TEX19 in cancer has not yet been defined.

METHODS: siRNA was used to deplete TEX19 levels in various cancer cell lines. This was extended using shRNA to deplete TEX19 in vivo. Western blotting, fluorescence activated cell sorting and immunofluorescence were used to study the effect of TEX19 depletion in cancer cells and to localize TEX19 in normal testis and cancer cells/tissues. RT-qPCR and RNA sequencing were employed to determine the changes to the transcriptome of cancer cells depleted for TEX19 and Kaplan-Meier plots were generated to explore the relationship between TEX19 expression and prognosis for a range of cancer types.

RESULTS: Depletion of TEX19 levels in a range of cancer cell lines in vitro and in vivo restricts cellular proliferation/self-renewal/reduces tumour volume, indicating TEX19 is required for cancer cell proliferative/self-renewal potential. Analysis of cells depleted for TEX19 indicates they enter a quiescent-like state and have subtle defects in S-phase progression. TEX19 is present in both the nucleus and cytoplasm in both cancerous cells and normal testis. In cancer cells, localization switches in a context-dependent fashion. Transcriptome analysis of TEX19 depleted cells reveals altered transcript levels of a number of cancer-/proliferation-associated genes, suggesting that TEX19 could control oncogenic proliferation via a transcript/transcription regulation pathway. Finally, overall survival analysis of high verses low TEX19 expressing tumours indicates that TEX19 expression is linked to prognostic outcomes in different tumour types.

CONCLUSIONS: TEX19 is required to drive cell proliferation in a range of cancer cell types, possibly mediated via an oncogenic transcript regulation mechanism. TEX19 expression is linked to a poor prognosis for some cancers and collectively these findings indicate that not only can TEX19 expression serve as a novel cancer biomarker, but may also offer a cancer-specific therapeutic target with broad spectrum potential.

LanguageEnglish
Article number84
JournalMolecular Cancer
Volume16
Issue number1
DOIs
StatusPublished - 26 Apr 2017

Fingerprint

Germ Cells
Stem Cells
Cell Proliferation
Genes
Neoplasms
Testicular Neoplasms
Neoplasm Genes
Tumor Biomarkers
Small Interfering RNA
Testis
RNA Sequence Analysis
Cell Line
Gene Expression Profiling
Survival Analysis
Tumor Burden
S Phase
Transcriptome
Fluorescent Antibody Technique
Flow Cytometry
Carcinogenesis

Keywords

  • Journal Article

Fields of Expertise

  • Human- & Biotechnology
  • Information, Communication & Computing

Treatment code (Nähere Zuordnung)

  • Basic - Fundamental (Grundlagenforschung)
  • Experimental

Cooperations

  • BioTechMed-Graz

Cite this

Planells-Palop, V., Hazazi, A., Feichtinger, J., Jezkova, J., Thallinger, G., Alsiwiehri, N. O., ... McFarlane, R. J. (2017). Human germ/stem cell-specific gene TEX19 influences cancer cell proliferation and cancer prognosis. Molecular Cancer, 16(1), [84]. DOI: 10.1186/s12943-017-0653-4

Human germ/stem cell-specific gene TEX19 influences cancer cell proliferation and cancer prognosis. / Planells-Palop, Vicente; Hazazi, Ali; Feichtinger, Julia; Jezkova, Jana; Thallinger, Gerhard; Alsiwiehri, Naif O; Almutairi, Mikhlid; Parry, Lee; Wakeman, Jane A; McFarlane, Ramsay J.

In: Molecular Cancer, Vol. 16, No. 1, 84, 26.04.2017.

Research output: Contribution to journalArticle

Planells-Palop, V, Hazazi, A, Feichtinger, J, Jezkova, J, Thallinger, G, Alsiwiehri, NO, Almutairi, M, Parry, L, Wakeman, JA & McFarlane, RJ 2017, 'Human germ/stem cell-specific gene TEX19 influences cancer cell proliferation and cancer prognosis' Molecular Cancer, vol 16, no. 1, 84. DOI: 10.1186/s12943-017-0653-4
Planells-Palop, Vicente ; Hazazi, Ali ; Feichtinger, Julia ; Jezkova, Jana ; Thallinger, Gerhard ; Alsiwiehri, Naif O ; Almutairi, Mikhlid ; Parry, Lee ; Wakeman, Jane A ; McFarlane, Ramsay J. / Human germ/stem cell-specific gene TEX19 influences cancer cell proliferation and cancer prognosis. In: Molecular Cancer. 2017 ; Vol. 16, No. 1.
@article{9230eff9979c4dc9bb7cb5922c1cc625,
title = "Human germ/stem cell-specific gene TEX19 influences cancer cell proliferation and cancer prognosis",
abstract = "BACKGROUND: Cancer/testis (CT) genes have expression normally restricted to the testis, but become activated during oncogenesis, so they have excellent potential as cancer-specific biomarkers. Evidence is starting to emerge to indicate that they also provide function(s) in the oncogenic programme. Human TEX19 is a recently identified CT gene, but a functional role for TEX19 in cancer has not yet been defined.METHODS: siRNA was used to deplete TEX19 levels in various cancer cell lines. This was extended using shRNA to deplete TEX19 in vivo. Western blotting, fluorescence activated cell sorting and immunofluorescence were used to study the effect of TEX19 depletion in cancer cells and to localize TEX19 in normal testis and cancer cells/tissues. RT-qPCR and RNA sequencing were employed to determine the changes to the transcriptome of cancer cells depleted for TEX19 and Kaplan-Meier plots were generated to explore the relationship between TEX19 expression and prognosis for a range of cancer types.RESULTS: Depletion of TEX19 levels in a range of cancer cell lines in vitro and in vivo restricts cellular proliferation/self-renewal/reduces tumour volume, indicating TEX19 is required for cancer cell proliferative/self-renewal potential. Analysis of cells depleted for TEX19 indicates they enter a quiescent-like state and have subtle defects in S-phase progression. TEX19 is present in both the nucleus and cytoplasm in both cancerous cells and normal testis. In cancer cells, localization switches in a context-dependent fashion. Transcriptome analysis of TEX19 depleted cells reveals altered transcript levels of a number of cancer-/proliferation-associated genes, suggesting that TEX19 could control oncogenic proliferation via a transcript/transcription regulation pathway. Finally, overall survival analysis of high verses low TEX19 expressing tumours indicates that TEX19 expression is linked to prognostic outcomes in different tumour types.CONCLUSIONS: TEX19 is required to drive cell proliferation in a range of cancer cell types, possibly mediated via an oncogenic transcript regulation mechanism. TEX19 expression is linked to a poor prognosis for some cancers and collectively these findings indicate that not only can TEX19 expression serve as a novel cancer biomarker, but may also offer a cancer-specific therapeutic target with broad spectrum potential.",
keywords = "Journal Article",
author = "Vicente Planells-Palop and Ali Hazazi and Julia Feichtinger and Jana Jezkova and Gerhard Thallinger and Alsiwiehri, {Naif O} and Mikhlid Almutairi and Lee Parry and Wakeman, {Jane A} and McFarlane, {Ramsay J}",
year = "2017",
month = "4",
day = "26",
doi = "10.1186/s12943-017-0653-4",
language = "English",
volume = "16",
journal = "Molecular Cancer",
issn = "1476-4598",
publisher = "BioMed Central",
number = "1",

}

TY - JOUR

T1 - Human germ/stem cell-specific gene TEX19 influences cancer cell proliferation and cancer prognosis

AU - Planells-Palop,Vicente

AU - Hazazi,Ali

AU - Feichtinger,Julia

AU - Jezkova,Jana

AU - Thallinger,Gerhard

AU - Alsiwiehri,Naif O

AU - Almutairi,Mikhlid

AU - Parry,Lee

AU - Wakeman,Jane A

AU - McFarlane,Ramsay J

PY - 2017/4/26

Y1 - 2017/4/26

N2 - BACKGROUND: Cancer/testis (CT) genes have expression normally restricted to the testis, but become activated during oncogenesis, so they have excellent potential as cancer-specific biomarkers. Evidence is starting to emerge to indicate that they also provide function(s) in the oncogenic programme. Human TEX19 is a recently identified CT gene, but a functional role for TEX19 in cancer has not yet been defined.METHODS: siRNA was used to deplete TEX19 levels in various cancer cell lines. This was extended using shRNA to deplete TEX19 in vivo. Western blotting, fluorescence activated cell sorting and immunofluorescence were used to study the effect of TEX19 depletion in cancer cells and to localize TEX19 in normal testis and cancer cells/tissues. RT-qPCR and RNA sequencing were employed to determine the changes to the transcriptome of cancer cells depleted for TEX19 and Kaplan-Meier plots were generated to explore the relationship between TEX19 expression and prognosis for a range of cancer types.RESULTS: Depletion of TEX19 levels in a range of cancer cell lines in vitro and in vivo restricts cellular proliferation/self-renewal/reduces tumour volume, indicating TEX19 is required for cancer cell proliferative/self-renewal potential. Analysis of cells depleted for TEX19 indicates they enter a quiescent-like state and have subtle defects in S-phase progression. TEX19 is present in both the nucleus and cytoplasm in both cancerous cells and normal testis. In cancer cells, localization switches in a context-dependent fashion. Transcriptome analysis of TEX19 depleted cells reveals altered transcript levels of a number of cancer-/proliferation-associated genes, suggesting that TEX19 could control oncogenic proliferation via a transcript/transcription regulation pathway. Finally, overall survival analysis of high verses low TEX19 expressing tumours indicates that TEX19 expression is linked to prognostic outcomes in different tumour types.CONCLUSIONS: TEX19 is required to drive cell proliferation in a range of cancer cell types, possibly mediated via an oncogenic transcript regulation mechanism. TEX19 expression is linked to a poor prognosis for some cancers and collectively these findings indicate that not only can TEX19 expression serve as a novel cancer biomarker, but may also offer a cancer-specific therapeutic target with broad spectrum potential.

AB - BACKGROUND: Cancer/testis (CT) genes have expression normally restricted to the testis, but become activated during oncogenesis, so they have excellent potential as cancer-specific biomarkers. Evidence is starting to emerge to indicate that they also provide function(s) in the oncogenic programme. Human TEX19 is a recently identified CT gene, but a functional role for TEX19 in cancer has not yet been defined.METHODS: siRNA was used to deplete TEX19 levels in various cancer cell lines. This was extended using shRNA to deplete TEX19 in vivo. Western blotting, fluorescence activated cell sorting and immunofluorescence were used to study the effect of TEX19 depletion in cancer cells and to localize TEX19 in normal testis and cancer cells/tissues. RT-qPCR and RNA sequencing were employed to determine the changes to the transcriptome of cancer cells depleted for TEX19 and Kaplan-Meier plots were generated to explore the relationship between TEX19 expression and prognosis for a range of cancer types.RESULTS: Depletion of TEX19 levels in a range of cancer cell lines in vitro and in vivo restricts cellular proliferation/self-renewal/reduces tumour volume, indicating TEX19 is required for cancer cell proliferative/self-renewal potential. Analysis of cells depleted for TEX19 indicates they enter a quiescent-like state and have subtle defects in S-phase progression. TEX19 is present in both the nucleus and cytoplasm in both cancerous cells and normal testis. In cancer cells, localization switches in a context-dependent fashion. Transcriptome analysis of TEX19 depleted cells reveals altered transcript levels of a number of cancer-/proliferation-associated genes, suggesting that TEX19 could control oncogenic proliferation via a transcript/transcription regulation pathway. Finally, overall survival analysis of high verses low TEX19 expressing tumours indicates that TEX19 expression is linked to prognostic outcomes in different tumour types.CONCLUSIONS: TEX19 is required to drive cell proliferation in a range of cancer cell types, possibly mediated via an oncogenic transcript regulation mechanism. TEX19 expression is linked to a poor prognosis for some cancers and collectively these findings indicate that not only can TEX19 expression serve as a novel cancer biomarker, but may also offer a cancer-specific therapeutic target with broad spectrum potential.

KW - Journal Article

U2 - 10.1186/s12943-017-0653-4

DO - 10.1186/s12943-017-0653-4

M3 - Article

VL - 16

JO - Molecular Cancer

T2 - Molecular Cancer

JF - Molecular Cancer

SN - 1476-4598

IS - 1

M1 - 84

ER -