The MicroRNA-200 Family Is Upregulated in Endometrial Carcinoma

Abstract

BackgroundMicroRNAs (miRNAs, miRs) are small non-coding RNAs that negatively regulate gene expression at the post-transcriptional level. MicroRNAs are dysregulated in cancer and may play essential roles in tumorigenesis. Additionally, miRNAs have been shown to have prognostic and diagnostic value in certain types of cancer. The objective of this study was to identify dysregulated miRNAs in endometrioid endometrial adenocarcinoma (EEC) and the precursor lesion, complex atypical hyperplasia (CAH).MethodologyWe compared the expression profiles of 723 human miRNAs from 14 cases of EEC, 10 cases of CAH, and 10 normal proliferative endometria controls using Agilent Human miRNA arrays following RNA extraction from formalin-fixed paraffin-embedded (FFPE) tissues. The expression of 4 dysregulated miRNAs was validated using real time reverse transcription-PCR.ResultsForty-three miRNAs were dysregulated in EEC and CAH compared to normal controls (p<0.05). The entire miR-200 family (miR-200a/b/c, miR-141, and miR-429) was up-regulated in cases of EEC.ConclusionsThis information contributes to the candidate miRNA expression profile that has been generated for EEC and shows that certain miRNAs are dysregulated in the precursor lesion, CAH. These miRNAs in particular may play important roles in tumorigenesis. Examination of miRNAs that are consistently dysregulated in various studies of EEC, like the miR-200 family, will aid in the understanding of the role that miRNAs play in tumorigenesis in this tumour type.

Diagnostic and prognostic significance of miRNA signatures in tissues and plasma of endometrioid endometrial carcinoma patients

“…[26][27][28][29][30] That might be due to different platform and normalization strategies used, as well as utilization of sample sets with various histological types, grade and clinical stage layouts. To reveal miRNA signatures characteristic exclusively for EEC, which is the most common type of endometrial malignancy, our study comprised cases with histologically proven endometrioid histology.…”

“…All miR-200 family members were significantly upregulated, which confirms results reported in few recently published studies. 26,29,30 Moreover, expression of those miRNAs was most pronounced in early clinical stages of EEC and a systematic decrease of their expression was noted in higher FIGO stages and in poorly differentiated tumors, which was significant in case of miR-200a, miR-200b* and miR-429. The role of miR-200 family (miR-141, miR-200a, miR-200b, miR-200c and miR-429) in EEC cancer has not been elucidated so far.…”

“…Contrary to this thesis upregulation of miR-200 family seem to constitute the most characteristic signature of EEC. 26,29,30 Moreover, an inhibition of miR-200 family members with anti-miRs resulted in attenuation of cell proliferation and cytotoxic effect in endometrial cancer HEC-1A and Ishikawa cell lines. 26 Such observations implicate an oncogenic potential of miR-200 in EEC.…”

Insights into the Diverse Roles of miR-205 in Human Cancers

“…A number of recent studies have investigated the expression profiles of miRNAs in endometrial cancer Cohn et al, 2010;Ratner et al, 2010;Snowdon et al, 2011). Several studies reported elevated expression level of miR-205 in different types of endometrial cancer compared to normal endometrial tissues and plasmas (Boren et al, 2008;Hiroki et al, 2010;Karaayvaz et al, 2012).…”

The role of micro-RNAs in the female reproductive tract

“…Of the current data, the miR-200 family is the most well studied. Snowdon et al (2011) reported that miR-200a/ b/c, miR-141, and miR-429 were upregulated in both endometrioid endometrial adenocarcinoma and complex atypical hyperplasia compared with normal control endometrium. Subsequent studies (Lee et al 2011, Park et al 2012 Three additional studies have evaluated the potential role of miRNAs in modulation of tumor suppressor genes in the context of endometrial adenocarcinomas.…”