Background:
LMS, an aggressive tumor, is a neoplasm of smooth muscle cells that arise in the uterus or in soft tissue throughout the body. LMS usually appears during para- menopause with poor prognosis.
ESS is a hormone-sensitive low-grade tumor, with infiltrating borders and a low-grade sarcoma appearance, ESS is often premenopausal with relatively good prognosis.
Currently, only limited therapeutic options exist for patients diagnosed with LMS or ESS and the lack of prognostic markers and limited understanding of the biological mechanism complicate the clinical management of these tumors.
Study Aims:
To examine the differentially expressed miRNA profile of primary and metastatic human uterine LMS lesions, and primary ESS lesions, and to evaluate the involvement of specific regulatory pathways.
Methods and Materials:
Eight primary and eight metastatic LMS and ESS lesions we analyzed using TaqMan low density miRNA array cards and bioinformatics tools were used to identify their predicted targets and the molecular networks they may affect.
Results:
MiRNA 15a and 92a were validated to be down regulated in metastatic LMS versus primary LMS (p < 0.05). Onto-Tools suite predicted 5 significant potential signaling pathways: TGF- β, Wnt, MAPK, Focal adhesion and mTOR.
MiRNA 31 was validated to be up regulated in metastatic LMS versus primary LMS (p < 0.05). Potential pathways were predicted: Wnt and MAPK.
6 miRNAs were validated to be down regulated in ESS in comparison to LMS (p < 0.05). Onto-Tools suite predicted the same pathways as in LMS: TGF- β, Wnt, MAPK, Focal adhesion and mTOR.
Analysis of gene expression array of the same samples revealed the activation of two common pathways: TGF-β and Wnt.
Conclusion:
To our knowledge, this is the first study evaluating the differential expression of miRNAs in LMS and ESS progression and proposes a potential target for future therapy of the diseases.
