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Open Access Highly Accessed Research article

Deregulation of miR-100, miR-99a and miR-199b in tissues and plasma coexists with increased expression of mTOR kinase in endometrioid endometrial carcinoma

Anna Torres12*, Kamil Torres13, Anna Pesci4, Marcello Ceccaroni56, Tomasz Paszkowski2, Paola Cassandrini7, Giuseppe Zamboni48 and Ryszard Maciejewski19

Author Affiliations

1 Laboratory of Biostructure, Chair and Department of Human Anatomy, Medical University of Lublin, Jaczewskiego 4, Lublin, Poland

2 III Chair and Department of Gynecology, Medical University of Lublin, Jaczewskiego 8, Lublin, Poland

3 General and Oncologic Surgery Department, Lublin County Specialist Hospital, Al. Kraśnicka 100, Lublin, Poland

4 Department of Pathology, Ospedale Sacro Cuore Don Calabria, Via don A. Sempreboni 5, Negrar, Verona, Italy

5 Gynecologic Oncology Division, International School of Surgical Anatomy, Ospedale Sacro Cuore Don Calabria, Via don A. Sempreboni 5, Negrar, Verona, Italy

6 Department of Obstetrics & Gynecology, European Gynecology Endoscopy School, Ospedale Sacro Cuore Don Calabria, Via don A. Sempreboni 5, Negrar, Verona, Italy

7 Department of Oncology, Ospedale Sacro Cuore Don Calabria, Via don A. Sempreboni 5, Negrar, Verona, Italy

8 Department of Pathology, University of Verona, Piazzale L.A. Scuro 10, 37134, Verona, Italy

9 II Chair and Department of Surgery, Medical University of Lublin, Staszica 16, 20-081, Lublin, Poland

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BMC Cancer 2012, 12:369  doi:10.1186/1471-2407-12-369

Published: 24 August 2012

Abstract

Background

Alterations of mTOR gene expression have been implicated in the pathogenesis of endometrioid endometrial cancer however only few studies explored the cause of increased mTOR activation in this malignancy. miRNAs are small, noncoding RNAs, which were proven to regulated gene expression at the posttranscriptional level. The study aimed to explore deregulation of miRNAs targeting mTOR kinase (miR-99a, miR-100 and miR-199b) as a possible cause of its altered expression in EEC tissues. In addition expression of the three miRNAs was investigated in plasma of EEC patients and was assessed in terms of diagnostic and prognostic utility.

Methods

We investigated expression of mTOR kinase transcripts in 46 fresh tissue samples. Expression of miR-99a, miR-100 and miR-199b was investigated in the same group of fresh samples, and in additional 58 FFPE sections as well as in 48 plasma samples using qPCR. Relative quantification was performed using experimentally validated endogenous controls.

Results

mTOR kinase expression was increased in EEC tissues and was accompanied by decreased expression of all three miRNAs. Down-regulation of the investigated miRNAs was discovered in plasma of EEC patients and miRNA signatures classified EEC tissues (miR-99a/miR-100/miR-199b) and plasma (miR-99a/miR-199b) samples with higher accuracy in comparison to single miRNAs. We also revealed that miR-100 was an independent prognostic marker of overall survival.

Conclusions

We conclude that increased expression of mTOR kinase coexists with down-regulation of its targeting miRNAs, which could suggest a new mechanism of mTOR pathway alterations in EEC. In addition, our findings implicate that miRNA signatures can be considered promising biomarkers for early detection and prognosis of endometrioid endometrial carcinoma.

Keywords:
mTOR; microRNA; miRNA; Endometrial cancer; Plasma