title: Major regulators of microRNAs biogenesis Dicer and Drosha are down-regulated in endometrial cancer.
abstract: Alterations in microRNAs expression have been proposed to play role in endometrial cancer pathogenesis. Dicer and Drosha are main regulators of microRNA biogenesis and deregulation of their expression has been indicated as a possible cause of microRNAs alterations observed in various cancers. The objective of this study was to investigate Dicer and Drosha genes expression in endometrial cancer and to analyze the impact of clinicopathological characteristics on their expression. Fresh tissue samples were collected from 44 patients (26 endometroid endometrial carcinoma and 18 controls). Clinical and pathological data were acquired from medical documentation. Dicer and Drosha genes expressions were assessed by qRT-PCR using validated reference genes. Dicer and Drosha expression levels were significantly lower in endometrial cancer samples comparing to controls. Dicer was down-regulated by the factor of 1.54 (p=0.009) and Drosha gene mean expression value was 1.4 times lower in endometrial cancer group versus control group (p=0.008). Down-regulation of Dicer significantly correlated with decreased expression of Drosha (coefficient value 0.75). Decreased expression of Drosha correlated with higher histological grade and was influenced by BMI. Lower Dicer expression was found in nulli- and uniparous females comparing to multiparous individuals (p=0.002). Neither the FIGO stage nor the menstrual status had significant influence on the expression of studied genes. This study revealed for the first time that expression alterations of main regulators of microRNAs biogenesis are present in endometrial cancer tissue and could be potentially responsible for altered microRNAs profiles observed in this malignancy.
authors.affiliation: Laboratory of Biostructure, Department of Human Anatomy, Medical University of Lublin, ul. Jaczewskiego 4, 20-094, Lublin, Poland. anna.torres@wp.pl
authors.forename: Anna
authors.initials: A
authors.lastname: Torres
authors.forename: Kamil
authors.initials: K
authors.lastname: Torres
authors.forename: Tomasz
authors.initials: T
authors.lastname: Paszkowski
authors.forename: Barbara
authors.initials: B
authors.lastname: Jodłowska-Jędrych
authors.forename: Tomasz
authors.initials: T
authors.lastname: Radomański
authors.forename: Andrzej
authors.initials: A
authors.lastname: Książek
authors.forename: Ryszard
authors.initials: R
authors.lastname: Maciejewski
mesh_terms: D015536:Down-Regulation; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D009367:Neoplasm Staging; D020133:Reverse Transcriptase Polymerase Chain Reaction; D043244:Ribonuclease III / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D035683:MicroRNAs; C517918:DROSHA protein, human; D043244:Ribonuclease III