Abstract
Endometrial cancer is the most common gynaecological cancer worldwide, and the prognosis of patients with advanced disease remains poor. MicroRNAs (miRs) are dysregulated in endometrial cancer. miRs-29-a, -b and -c expression levels are downregulated in endometrial cancer; however, a specific role for miR-29c and its target genes remain to be elucidated. The aim of the present study was to determine the functional effect of restoring miR-29c expression in endometrial cancer cell lines and to identify miR-29c targets involved in cancer progression. miR-29c expression in human endometrial tumour grades 1-3 and benign tissue as well as in the endometrial cancer cell lines Ishikawa, HEC1A and AN3CA were analysed using reverse transcriptase-quantitative PCR (RT-qPCR). The cell lines were transfected with miR-29c mimic, miR-29c inhibitor or scrambled control. xCELLigence real-time cell monitoring analysed proliferation and migration, and flow cytometry was used to analyse apoptosis and cell cycle. The expression of miR-29c target genes in transfected cell lines was analysed using RT-qPCR. miR-29c was downregulated in grade 1-3 endometrial cancer samples compared with benign endometrium. miR-29c was reduced in Ishikawa and AN3CA cells, but not in HEC1A cell lines compared with non-cancerous primary human endometrial epithelial cells. Overexpression of miR-29c variably reduced proliferation, increased apoptosis and reduced the expression levels of miR-29c target genes, including cell division cycle 42, HMG-box transcription factor 1, integrin subunit β 1, MCL1 apoptosis regulator BCL2 family member, MDM2 proto-oncogene, serum/glucocorticoid regulated kinase 1, sirtuin 1 and vascular endothelial growth factor A, across the three cell lines investigated. Inhibition of miR-29c in HEC1A cells increased proliferation and collagen type IV α 1 chain expression. The re-introduction of miR-29c to endometrial cancer cell lines reduced proliferation, increased apoptosis and reduced miR-29c target gene expression in vitro. The present results suggested that miR-29c may be a potential therapeutic target for endometrial cancer.