The long non-coding RNA (lncRNA), HAR1A is emerging as a putative tumour suppressor.
In non-neoplastic brain cells, REST suppresses HAR1A expression. In gliomas REST acts
as an oncogene and is a potential therapeutic target. It is therefore conceivable
that REST promotes glioma progression by down-regulating HAR1A . To test this hypothesis,
glioma clinical databases were analysed to study: (I) HAR1A / REST correlation; (II)
HAR1A and REST prognostic role; (III) molecular pathways associated with these genes.
HAR1A expression and subcellular localization were studied in glioblastoma and paediatric
glioma cells. REST function was also studied in these cells, by observing the effects
of gene silencing on: (I) HAR1A expression; (II) cancer cell proliferation, apoptosis,
migration; (III) expression of neural differentiation genes. The same phenotypes (and
cell morphology) were studied in HAR1A overexpressing cells. Our results show that
REST and HAR1A are negatively correlated in gliomas. Higher REST expression predicts
worse prognosis in low-grade gliomas (the opposite is true for HAR1A ). REST -silencing
induces HAR1A upregulation. HAR1A is primarily detected in the nucleus. REST -silencing
dramatically reduces cell proliferation and induces apoptosis, but HAR1A overexpression
has no major effect on investigated cell phenotypes. We also show that REST regulates
the expression of neural differentiation genes and that its oncogenic function is
primarily HAR1A -independent.
