MicroRNA-125b down-regulation mediates endometrial cancer invasion by targeting ERBB2

Background:    MicroRNAs (miRNAs) are small non-coding nucleotides that regulate mRNA stability and protein expression by imperfect base pairing with the 3’-untranslated region (3’UTR) of target mRNAs. Many miRNAs have been documented to be aberrantly expressed in human cancers, but the role of miRNAs in endometrioid endometrial cancer (EEC) remains poorly understood. The objective of this study was to investigate the effect of miR-125b on EEC development and to explore its molecular mechanism in EEC carcinogenesis.
    Material/Methods:    Real-time quantitative PCR was applied to evaluate the expression level of miRNA-125b in EEC and normal endometrium (NE) samples. The invasion ability of miR-125b in EEC HEC1B cells was analyzed by Transwell assay after pre-miR-125b or anti-miR-125b transfection. For the invasion mechanism analysis of miR-125b on HEC1B cells, miRBase, TargetScan, miRanda and PicTar were used to predict the possible target gene of miR-125b. Luciferase activities assay, cotransfection and Western blot were used to reveal that the predicted target genes of miR-125b were direct and specific. RNA interference technology was used to confirm that the invasion inhibition of miR-125b was directly induced by ERBB2.
    Results:    Our study showed that miR-125b was down-regulated in human EEC specimens compared to that in NC specimens. Over-expression of miR-125b in HEC1B cells inhibited EEC invasion and this inhibitory effect on HEC1B cells could be restored by miR-125b knock down. Mechanism analysis revealed that ERBB2 was a direct and specific target of miR-125b. The inhibitory effect on EEC cell invasion was mediated by miR-125b inhibition of the translation of a proto-oncogene, ERBB2.
    Conclusions:    Aberrantly expressed miR-125b contributes to HEC1B cells invasion partly through directly down-regulating ERBB2 protein expression in EEC. This miRNA signature offers a novel potential therapeutic strategy for EEC.

Keywords: Molecular Sequence Data, MicroRNAs - metabolism, Gene Expression Regulation, Neoplastic, Endometrial Neoplasms - pathology, Down-Regulation - genetics, Cell Line, Tumor, Base Sequence, 3' Untranslated Regions - genetics, Neoplasm Invasiveness, Receptor, erbB-2 - metabolism, Reproducibility of Results