No abstract

Epithelial-mesenchymal transition (EMT) has been shown to exert promoting effects on the progression of a number of cancer types, including endometrial carcinoma (EC). MicroRNA (miRNA or miR)-195 has been shown to function as a tumor suppressor. This study aimed to explore the potential role of miR-195 in the EMT process of EC. miR-195 overexpression (Mimics) and mimics control (Mock) vectors were constructed and transfected into human endometrial cancer cells (AN3-CA and Hec1A) using Lipofectamine 2000, and cell viability was detected using the Cell Counting kit-8 (CCK-8). The invasive and migratory capacities of the cells transfected with the Mimics or Mock vectors were assessed by Transwell and wound healing assays. Relative mRNA and protein levels were analyzed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis, respectively. Using TargetScan prediction, the potential target of miR-195 was identified and was further verified by dual-luciferase reporter assay. Following transfection with miR-195 mimics, the viability of the AN3-CA and Hec1A cells decreased in a time-dependent manner, specifically at 24 h. The wound closure rate and the number of invaded cells in the Mimics group were much lower than those in the Control and Mock groups (P<0.01). miR-195 overexpression significantly upregulated the mRNA and protein levels of tissue inhibitor of metalloproteinase 2 (TIMP-2), while it downregulated the expression levels of matrix metalloproteinase (MMP)-2 and MMP-9. Moreover, the phosphorylation levels of PI3K and AKT were also notably decreased (P<0.01). G protein-coupled estrogen receptor 1 (GPER) was identified as a target of miR-195. On the whole, the findings of this study indicate that the inhibitory effects of miR195 on EC cell migration and invasion are associated with the PI3K/AKT signaling pathway and GPER expression.

Background: Potential anti-tumor effects of microRNA-497 (miR-497) have been highlighted in various malignancies including breast cancer. However, little is known about the function of miR-497 and its putative target mucin1 (MUC1) in breast cancer. The present study explored how miR-497 regulates breast cancer progression in a MUC1-dependent manner. Methods: Expression of miR-497 and MUC1 was determined in breast cancer tissues and cells. Methylation specific polymerase chain reaction was used to measure the methylation status of CpG islands of miR-497 promoter, while chromatin immunoprecipitation assay was used to detect recruitment of methyltransferase to the promoter region of miR-497. Alteration in expression of miR-497 (overexpression) and MUC1 (up-and down-regulation) was performed to examine their roles in breast cancer biology in vitro and in vivo. The binding affinity between miR-497 and MUC1 was investigated through a bioinformatics database and dual luciferase reporter gene assay. Results: MiR-497 was down-regulated and MUC1 was up-regulated in breast cancer tissues and cell lines. Besides, methylation induced a down-regulation of miR-497 in breast cancer. The bioinformatics analysis and dual luciferase reporter gene assay indicated that miR-497 targeted MUC1. Overexpression of miR-497 inhibited breast cancer cell proliferation and invasion and promoted the apoptosis of breast cancer cells by down-regulating MUC1. The inhibitory action of miR-497 on tumor growth was validated in vivo. Conclusion: In conclusion, miR-497 down-regulated MUC1 expression and subsequently suppressed breast cancer progression, highlighting miR-497 to be a potential biomarker and therapeutic target for breast cancer therapy.

Bacterial vaginosis (BV) is a common type of vaginitis. Berberine is a natural alkaline product that reduces oxidative stress and apoptosis in cells. The aim of the present study was to investigate the effects of berberine on oxidative stress and apoptotic rates of BV. Vaginal epithelial and discharge samples were obtained from 60 healthy individuals and 180 patients with BV before and after one month of berberine treatment. Clinical observation was documented for all patients before and after treatment for comparison. Additionally, an in vitro study was performed; the samples were divided into groups the following groups: Control, model (H 2 O 2 -treated), LT (low-dose berberine), MT (medium-dose berberine) and HT (high-dose berberine). Expression levels of the oxidative stress related proteins were detected by western blotting. Clinical symptoms of patients with BV significantly improved following berberine treatment. Oxidative stress in vaginal discharge was significantly lower following treatment, indicated by the increased activity of superoxide dismutase (SOD) and catalase, as well as the reduced levels of malondialdehyde and H 2 O 2 . Apoptosis of the vaginal epithelial cells was also reduced, which was indicated by the reduced expression of apoptosis proteins caspase-3, cytochrome C, capase-12 and Bax, and increased expression of Bcl-2. The results of the in vitro experiments demonstrated a dose-dependent decrease in apoptosis with berberine treatment compared with levels before treatment. Oxidative stress relief was demonstrated by the reduced reactive oxygen species level and increased SOD and endothelial nitric oxide synthase levels, whereas suppression of apoptosis was further supported by the reduction in apoptotic proteins, as well as a decreased Bax/Bcl-2 ratio. Berberine exhibited effects on lowering oxidative stress in vaginal discharge and reducing oxidative damage, as well as apoptosis of the vaginal epithelium, which are beneficial to patients with bacterial vaginosis.