MicroRNA-30c (miR-30c) has been reported to be a tumour suppressor in endometrial cancer (EC). We demonstrate that miR-30c is down-regulated in EC tissue and is highly expressed in estrogen receptor (ER)-negative HEC-1-B cells. MiR-30c directly inhibits MTA-1 expression and functions as a tumour suppressor via the miR-30c-MTA-1 signalling pathway. Furthermore, miR-30c is decreased upon E₂ treatment in both ER-positive Ishikawa and ER-negative HEC-1-B cells. Taken together, our results suggest that miR-30c is an important deregulated miRNA in EC and might serve as a potential biomarker and novel therapeutic target for EC.

Cervical cancer is one of the most prevalent gynecologic malignancies and has remained an intractable cancer over the past decades. We analyzed the aberrant expression patterns of cervical cancer using RNA-Seq data from The Cancer Genome Atlas (TCGA). A total of 3352 differently expressed genes (DEGs) were identified in 306 cervical cancer samples compared with 3 control samples, with 1401 genes upregulated and 1951 downregulated. Under Kaplan–Meier analysis, 76 out of these DEGs with a significantly different survival rate between patients with high and low expression groups were picked out and uploaded to perform Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, which identified a transferrin receptor (TFRC)-involved HIF-1 signaling pathway (p < 0.05). Clinical data analysis showed that high TFRC expression in cervical cancers was associated with incrementally advanced stage, tumor status, and lymph nodes (all p-values <0.05), while multivariate analysis revealed that TFRC remained an independent prognostic variable for poor overall survival. In conclusion, our data indicated that the TFRC-involved HIF-1 signaling pathway may play a crucial role in cervical cancer.

Despite improvements in treatment over the past few decades, endometrial cancer remains one of the most common causes of mortality in women and there is an urgent need for the development of targeted therapies. The aim of this study was to confirm the target gene of miR-103 in human endometrial cancer and investigate the biological functions in which miR-103 is involved through the regulation of the expression of its target gene. This study may provide useful data to gain a better understanding of the effect of miR-103 in tumor formation. miR-103 expression levels were measured using real-time quantitative PCR. The effect of miR-103 on tissue inhibitor of metalloproteinase 3 (TIMP-3) expression was assessed in endometrial cancer cell lines with a miR-103 inhibitor to decrease the level of miR-103 expression. Furthermore, the roles of miR-103 in cell growth and invasion were analyzed using miR-103 inhibitor-transfected cells. The level of expression of miR-103 decreased following transfection with the miR-103 inhibitor. miR-103 inhibitor transfection increased the activity of the luciferase reporter assay containing the TIMP-3 3’-untranslated region (UTR) construct and increased the levels of the TIMP-3 protein but not its mRNA in endometrial cancer cell lines. Finally, miR-103 inhibitor-transfected cells exhibited reduced cell growth and invasive characteristics. Our data suggested that miR-103 post-transcriptionally downregulates the expression of the tumor suppressor TIMP-3 and stimulates growth and invasion in endometrial cancer cell lines. This provides a possible therapeutic target that may upregulate TIMP-3 in endometrial cancer.

Disruptions of angiogenesis can have a significant effect on the healing of uterine scars. Human endometrial perivascular cells (CD146+PDGFRβ+) function as stem cells in the endometrium. Cysteine-rich angiogenic inducer 61 (CYR61) plays an important role in vascular development. The purpose of this study was to observe the effects of the transplantation of human endometrial perivascular cells (En-PSCs) overexpressing CYR61 on structural and functional regeneration in rat models of partial full-thickness uterine excision. We first sorted human En-PSCs from endometrial single-cell suspensions by flow cytometry. Human En-PSCs expressing low or high levels of CYR61 were then generated via transfection with a CYR61-specific small interfering ribonucleic acid (si-CYR61) construct or overexpression plasmid. To establish a rat model of uterine injury, a subset of uterine wall was then resected from each uterine horn in experimental animals. Female rats were randomly assigned to five groups, including a sham-operated group and four repair groups that received either PBS loaded on a collagen scaffold (collagen/PBS), En-PSCs loaded on a collagen scaffold (collagen/En-PSCs), En-PSCs with low CYR61 expression loaded on a collagen scaffold (collagen/si-CYR61 En-PSCs), and En-PSCs overexpressing CYR61 loaded on a collagen scaffold (collagen/ov-CYR61 En-PSCs). These indicated constructs were sutured in the injured uterine area to replace the excised segment. On days 30 and 90 after transplantation, a subset of rats in each group was sacrificed, and uterine tissue was recovered and serially sectioned. Hematoxylin and eosin staining and immunohistochemical staining were then performed. Finally, the remaining rats of each group were mated with fertile male rats on day 90 for a 2-week period. Sorted En-PSCs expressed all recognized markers of mesenchymal stem cells (MSCs), including CD10, CD13, CD44, CD73, CD90, and CD105, and exhibited differentiation potential toward adipocytes, osteoblasts, and neuron-like cells. Compared with En-PSCs and En-PSCs with low CYR61 expression, En-PSCs with elevated CYR61 expression enhanced angiogenesis by in vitro co-culture assays. At day 90 after transplantation, blood vessel density in the collagen/ov-CYR61 En-PSCs group (11.667 ± 1.287) was greater than that in the collagen/En-PSCs group (7.167 ± 0.672) (P < 0.05) and the collagen/si-CYR61 En-PSCs group (3.750 ± 0.906) (P < 0.0001). Pregnancy rates differed among groups, from 40% in the collagen/PBS group to 80% in the collagen/En-PSCs group, 12.5% in the collagen/si-CYR61 En-PSCs group, and 80% in the collagen/ov-CYR61 En-PSCs group. In addition, four embryos were evident in the injured uterine horns of the collagen/ov-CYR61 En-PSCs group, while no embryos were identified in the injured uterine horns of the collagen/PBS group. The results showed that CYR61 plays an important role in angiogenesis. Collagen/ov-CYR61 En-PSCs promoted endometrial and myometrial regeneration and induced neovascular regeneration in injured rat uteri. The pregnancy rate of rats treated with transplantation of collagen/En-PSCs or collagen/ov-CYR61 En-PSCs was improved. Moreover, the number of embryos implantation on the injured area in uterus was increased after transplantation of collagen/ov-CYR61 En-PSCs.

Background: long noncoding RNA (lncRNA) has been widely studied and understood in various cancer types. However, the expression profiles of glycolysis-related lncRNA in endometrial cancer (EC) have poorly been reported.