The effect of HES6 silencing on the gene expression profiles of the glioblastoma A172 and LN405 cell lines

ABSTRACT: Malignant glioma is the most common type of primary brain tumor diagnosed annually in 16,000 individuals in the United States. We performed a systematic large-scale transcriptomics data mining study of 9,783 Affymetrix samples from the GeneSapiens database in order to identify those genes that are most glioma-specific as compared to other cancers and normal tissues. We searched for genes that are highly expressed in 322 glioblastoma multiforme tissue samples and 66 anaplastic astrocytomas as compared to 425 samples from histologically normal central nervous system. Transcription cofactor HES6 (Hairy and Enhancer of Split 6) emerged as one of the most glioma-specific genes. In immunostaining of a tissue microarray series, HES6 was expressed in 335 (98.8%) out of the 339 clinical glioma samples. Recurrent grade 2 astrocytomas and grade 2-3 oligodendrogliomas showed higher levels of HES6 immunoreactivity than the corresponding primary tumors. Functional studies implied a critical role for HES6 in supporting survival of glioma cells, as evidenced by 60% reduced cancer cell viability and induction of Caspase 3/7 activity after HES6 silencing by RNA interference in A172 and LN405 cells. The biological role and consequences of HES6 silencing and overexpression was explored with genome-wide analyses, which indicated a key role for HES6 in e.g. p53, c-myc, and NF-?B transcriptional networks. We conclude that HES6 has a critical role in sustaining glioma cell growth, survival, migration and possibly angiogenesis. HES6 is a potential therapeutic target and biomarker for glioma.

ORGANISM(S): Homo sapiens

PROVIDER: GSE22692 | GEO | 2011/06/30

SECONDARY ACCESSION(S): PRJNA128299

REPOSITORIES: GEO