Integrative miRnome and transcriptome analysis in human malignant prolactin pituitary tumors identify miR-183 as driving gene for tumor progression to malignancy.

ABSTRACT: miRNAs expression is known to be deregulated in many types of cancer leading to suspect them implication in crucial steps occurring during tumor progression and maybe as potential driving genes. In this study we tried to decipher the place of miRNA in the hierarchical events cascade occurring in prolactinoma-tumours progression toward malignancy by using an integrative genomic approach performed on the same samples associating global miRNA expression, transcriptomic, DNA structure and methylation analyses. By this approach, we observed the down-regulation of 3 miRNAs (miR-183, miR-98, and miR-744) in A vs. NA tumors. MiR-98 and miR-744 were demonstrated to regulate respectively E2F2 and TGFB1 which are up-regulated in the A vs. NA prolactinomas. Moreover we demonstrated that KIAA0101 is a new target of miR-183 and that miR-183 is regulated by the transcription factor ETS2. KIAA0101 is up-regulated in the A vs. NA prolactinomas. KIAA0101, E2F2 and TGFB1 are interconnected in a pathway controlling cell proliferation and invasion that is over-activated in A PRL tumors. Thus the down-regulation of these three miRNAs is involved in the tumoral progression of human prolactinoma towards aggressiveness. The integrative genomic approach used here allowed us to propose a model of PRL tumoral progression towards aggressiveness. Moreover it revealed the potential of integrative genomic strategy applied in the same human tumors to identify the molecular mechanisms responsible for tumor progression even from a small cohort of patients. miRNA signatures was assessed on 4 aggressive, 8 non-aggressive human prolactin secreting pituitary tumors and 1 normal pituitary for data normalization.

ORGANISM(S): Homo sapiens

SUBMITTER: magali roche 

PROVIDER: E-GEOD-46294 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress