HES6 gene is selectively overexpressed in glioma and represents an important transcriptional regulator of glioma proliferation

Saija Haapa-Paananen (Corresponding Author), S. Kiviluoto, M. Waltari, M. Puputti, John Mpindi, Pekka Kohonen, O. Tynninen, H. Haapasalo, H. Joensuu, Merja Perälä, Olli Kallioniemi

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Abstract

Malignant glioma is the most common brain tumor with 16 000 new cases diagnosed annually in the United States. We performed a systematic large-scale transcriptomics data mining study of 9783 tissue samples from the GeneSapiens database to systematically identify genes that are most glioma-specific. We searched for genes that were highly expressed in 322 glioblastoma multiforme tissue samples and 66 anaplastic astrocytomas as compared with 425 samples from histologically normal central nervous system. Transcription cofactor HES6 (hairy and enhancer of split 6) emerged as the most glioma-specific gene. Immunostaining of a tissue microarray showed HES6 expression in 335 (98.8%) out of the 339 glioma samples. HES6 was expressed in endothelial cells of the normal brain and glioma tissue. Recurrent grade 2 astrocytomas and grade 2 or 3 oligodendrogliomas showed higher levels of HES6 immunoreactivity than the corresponding primary tumors. High HES6 mRNA expression correlated with the proneural subtype that generally has a favorable outcome but is prone to recur. Functional studies suggested an important role for HES6 in supporting survival of glioma cells, as evidenced by reduction of cancer cell proliferation and migration after HES6 silencing. The biological role and consequences of HES6 silencing and overexpression was explored with genome-wide analyses, which implicated a role for HES6 in p53, c-myc and nuclear factor-κB transcriptional networks. We conclude that HES6 is important for glioma cell proliferation and migration, and may have a role in angiogenesis.
Original languageEnglish
Pages (from-to)1299-1310
JournalOncogene
Volume31
Issue number10
DOIs
Publication statusPublished - 2012
MoE publication typeA1 Journal article-refereed

Fingerprint

Glioma
Genes
Astrocytoma
Cell Movement
Cell Proliferation
Oligodendroglioma
Data Mining
Gene Regulatory Networks
Glioblastoma
Brain Neoplasms
Neoplasms
Cell Survival
Central Nervous System
Endothelial Cells
Genome
Databases
Messenger RNA
Brain

Keywords

  • HES6
  • glioma
  • astrocytoma
  • glioblastoma
  • TMA
  • RNAi

Cite this

Haapa-Paananen, S., Kiviluoto, S., Waltari, M., Puputti, M., Mpindi, J., Kohonen, P., ... Kallioniemi, O. (2012). HES6 gene is selectively overexpressed in glioma and represents an important transcriptional regulator of glioma proliferation. Oncogene, 31(10), 1299-1310. https://doi.org/10.1038/onc.2011.316
Haapa-Paananen, Saija ; Kiviluoto, S. ; Waltari, M. ; Puputti, M. ; Mpindi, John ; Kohonen, Pekka ; Tynninen, O. ; Haapasalo, H. ; Joensuu, H. ; Perälä, Merja ; Kallioniemi, Olli. / HES6 gene is selectively overexpressed in glioma and represents an important transcriptional regulator of glioma proliferation. In: Oncogene. 2012 ; Vol. 31, No. 10. pp. 1299-1310.
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Haapa-Paananen, S, Kiviluoto, S, Waltari, M, Puputti, M, Mpindi, J, Kohonen, P, Tynninen, O, Haapasalo, H, Joensuu, H, Perälä, M & Kallioniemi, O 2012, 'HES6 gene is selectively overexpressed in glioma and represents an important transcriptional regulator of glioma proliferation', Oncogene, vol. 31, no. 10, pp. 1299-1310. https://doi.org/10.1038/onc.2011.316

HES6 gene is selectively overexpressed in glioma and represents an important transcriptional regulator of glioma proliferation. / Haapa-Paananen, Saija (Corresponding Author); Kiviluoto, S.; Waltari, M.; Puputti, M.; Mpindi, John; Kohonen, Pekka; Tynninen, O.; Haapasalo, H.; Joensuu, H.; Perälä, Merja; Kallioniemi, Olli.

In: Oncogene, Vol. 31, No. 10, 2012, p. 1299-1310.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - HES6 gene is selectively overexpressed in glioma and represents an important transcriptional regulator of glioma proliferation

AU - Haapa-Paananen, Saija

AU - Kiviluoto, S.

AU - Waltari, M.

AU - Puputti, M.

AU - Mpindi, John

AU - Kohonen, Pekka

AU - Tynninen, O.

AU - Haapasalo, H.

AU - Joensuu, H.

AU - Perälä, Merja

AU - Kallioniemi, Olli

PY - 2012

Y1 - 2012

N2 - Malignant glioma is the most common brain tumor with 16 000 new cases diagnosed annually in the United States. We performed a systematic large-scale transcriptomics data mining study of 9783 tissue samples from the GeneSapiens database to systematically identify genes that are most glioma-specific. We searched for genes that were highly expressed in 322 glioblastoma multiforme tissue samples and 66 anaplastic astrocytomas as compared with 425 samples from histologically normal central nervous system. Transcription cofactor HES6 (hairy and enhancer of split 6) emerged as the most glioma-specific gene. Immunostaining of a tissue microarray showed HES6 expression in 335 (98.8%) out of the 339 glioma samples. HES6 was expressed in endothelial cells of the normal brain and glioma tissue. Recurrent grade 2 astrocytomas and grade 2 or 3 oligodendrogliomas showed higher levels of HES6 immunoreactivity than the corresponding primary tumors. High HES6 mRNA expression correlated with the proneural subtype that generally has a favorable outcome but is prone to recur. Functional studies suggested an important role for HES6 in supporting survival of glioma cells, as evidenced by reduction of cancer cell proliferation and migration after HES6 silencing. The biological role and consequences of HES6 silencing and overexpression was explored with genome-wide analyses, which implicated a role for HES6 in p53, c-myc and nuclear factor-κB transcriptional networks. We conclude that HES6 is important for glioma cell proliferation and migration, and may have a role in angiogenesis.

AB - Malignant glioma is the most common brain tumor with 16 000 new cases diagnosed annually in the United States. We performed a systematic large-scale transcriptomics data mining study of 9783 tissue samples from the GeneSapiens database to systematically identify genes that are most glioma-specific. We searched for genes that were highly expressed in 322 glioblastoma multiforme tissue samples and 66 anaplastic astrocytomas as compared with 425 samples from histologically normal central nervous system. Transcription cofactor HES6 (hairy and enhancer of split 6) emerged as the most glioma-specific gene. Immunostaining of a tissue microarray showed HES6 expression in 335 (98.8%) out of the 339 glioma samples. HES6 was expressed in endothelial cells of the normal brain and glioma tissue. Recurrent grade 2 astrocytomas and grade 2 or 3 oligodendrogliomas showed higher levels of HES6 immunoreactivity than the corresponding primary tumors. High HES6 mRNA expression correlated with the proneural subtype that generally has a favorable outcome but is prone to recur. Functional studies suggested an important role for HES6 in supporting survival of glioma cells, as evidenced by reduction of cancer cell proliferation and migration after HES6 silencing. The biological role and consequences of HES6 silencing and overexpression was explored with genome-wide analyses, which implicated a role for HES6 in p53, c-myc and nuclear factor-κB transcriptional networks. We conclude that HES6 is important for glioma cell proliferation and migration, and may have a role in angiogenesis.

KW - HES6

KW - glioma

KW - astrocytoma

KW - glioblastoma

KW - TMA

KW - RNAi

U2 - 10.1038/onc.2011.316

DO - 10.1038/onc.2011.316

M3 - Article

VL - 31

SP - 1299

EP - 1310

JO - Oncogene

JF - Oncogene

SN - 0950-9232

IS - 10

ER -