Altered MicroRNA Expression Profile in Human Pituitary GH Adenomas: Down-Regulation of miRNA Targeting HMGA1, HMGA2, and E2F1

Abstract

Our study identifies a specific subset of miRNA, whose down-regulation might contribute to pituitary tumorigenesis.

Epidrug mediated re-expression of miRNA targeting the HMGA transcripts in pituitary cells

“…[11] In those cases where we observed decrease in miRNA transcript levels, ChIP analysis showed, in the majority of cases, depletion of the modification associated with active genes, H3K9Ac, and enrichment for the modification associated with silences genes, H3K27me3, relative to post-mortem pituitaries ( Figure 1B and 1C, and supplemental Figure S1B and S1C, respectively). Distinct from these findings, and in agreement with a previous report [14], increased expression of miR-320, confined to GH secreting adenoma was apparent (supplemental Fig. S1A).…”

“…Contrary to these findings, expression of miR-320 is increased in GH secreting adenoma and depleted in other adenoma subtypes and similar findings of subtype specific expression patterns have been reported elsewhere. [14] Moreover, and reinforcing these observations we now show that increased expression of miR-320 is associated with histone modification that characterize transcribed gene. Collectively, these findings would suggest that histone tail modifications impact on chromatin remodeling and miRNA expression.…”

“…[11] these authors employed heterologous expression vectors harbouring each of the precursor miRNA. [11] Moreover, in this and in subsequent reports ( [14,45] they also provide evidence that enforced expression of miRNA impact on mRNA stability and inhibition of translation. Using a quantitative ELISA based assay, specific for rodent hmga1, our data also shows that epidrugs lead to decrease in hmga1 protein.…”

“…[11] In a follow on study, in this case interrogating GH secreting adenoma, multiple miRNA that target the HMGA and the E2F1 transcripts were also identified and their heterologous expression were also associated with similar end-points. [14] More recent studies, of inappropriate miRNA expression profile in this case in GH and ACTH secreting adenomas also show that particular miRNA can elicit growth suppressive actions in vitro, and also in, in vivo model systems. [15,16] Collectively, these reports portend the therapeutic potential of miRNA through either restoration or inhibition of their expression in tumour cells.…”

“…[14] MiRNA sequences, their specific transcription start sites and, where present, their associated CpG islands, were determined using the, miRBase, miRStart and miRT databases. [21][22][23] Expression Analysis:…”