Ewelina Hermyt

Expression pattern of circadian rhythm-related genes and its potential relationship with miRNAs activity in endometrial cancer

The circadian clock is an autonomous oscillator that controls key aspects of cell physiology, including metabolism, transcriptional state, and cell signaling. Disturbances of circadian rhythms lead to disruption of cell and tissue homeostasis, which promotes carcinogenesis. The aim of the study was to determine the expression of circadian rhythm-related genes in endometrial cancer and to select miRNAs involved in the regulation of their expression. 50 endometrial tissue samples were collected from patients who underwent hysterectomy: 40 diagnosed with endometrial cancer and 10 without cancer. Expression profile of circadian rhythm-related genes was evaluated using microarrays and validated with RT-qPCR. MicroRNA expression was assessed using microarrays. Then mirTAR tool was used to identify miRNAs involved in the expression regulation of circadian rhythm-related genes. CLOCK expression is disrupted in endometrial cancer, which may be due to miR-15b, miR-331-3p and miR-200a overexpression. Elevated NPAS2 and CSNK1D levels may be associated with miR-432 silencing. In addition, high miR-874 and miR-200a expression may be potentially responsible for the reduction of PER3 level. Change of CLOCK, CSNK1D, NPAS2 and PER3 expression may suggest that circadian rhythms are disrupted in endometrial cancer. A possible mechanism of the observed changes may be related to miRNAs activity.

miRNAs Participate in the Regulation of Oxidative Stress-Related Gene Expression in Endometrioid Endometrial Cancer

Reactive oxygen species are formed as by-products of normal cell metabolism. They are needed to maintain cell homeostasis and signaling, which is possible due to defense systems. Disruption of this balance leads to oxidative stress that can induce cancer. Redox regulation by miRNAs may be a potential therapeutic target. The aim of the study was to assess the activity of genes associated with oxidative stress in endometrial cancer and to determine their relationship with miRNAs. The study included 45 patients with endometrioid endometrial cancer and 45 without neoplastic changes. The expression profile of genes associated with oxidative stress was determined with mRNA microarrays, RT-qPCR and ELISA. The miRNA prediction was performed based on the miRNA microarray experiment and the mirDB tool. PRDX2 and AQP1 showed overexpression that was probably not related to miRNA activity. A high level of PKD2 may be the result of a decrease in the activity of miR-195-3p, miR-20a, miR-134. A SOD3 level reduction can be caused by miR-328, miR-363. In addition, miR-363 can also regulate KLF2 expression. In the course of endometrial cancer, the phenomenon of oxidative stress is observed, the regulation of which may be influenced by miRNAs.

Recent Multiomics Approaches in Endometrial Cancer

Endometrial cancer is the most common gynecological cancers in developed countries. Many of the mechanisms involved in its initiation and progression remain unclear. Analysis providing comprehensive data on the genome, transcriptome, proteome, and epigenome could help in selecting molecular markers and targets in endometrial cancer. Multiomics approaches can reveal disturbances in multiple biological systems, giving a broader picture of the problem. However, they provide a large amount of data that require processing and further integration prior to analysis. There are several repositories of multiomics datasets, including endometrial cancer data, as well as portals allowing multiomics data analysis and visualization, including Oncomine, UALCAN, LinkedOmics, and miRDB. Multiomics approaches have also been applied in endometrial cancer research in order to identify novel molecular markers and therapeutic targets. This review describes in detail the latest findings on multiomics approaches in endometrial cancer.